Secondary respiratory infections appear to be highly prevalent among patients with severe COVID-19, but at this point, most pulmonologists aren’t sure what to make of this understudied phenomenon.

“We really do not understand the implications of secondary infections on outcomes in COVID-19 patients,” David L. Bowton, MD, FCCP, said in an interview. “In most early reports the incidence of secondary infections was much higher in patients dying from COVID-19, compared to survivors, but it isn’t clear whether this indicates that the secondary infection itself led to excess mortality or was more a marker of the severity of the COVID-19 infection.

“Further, details of the diagnostic criteria used, the microbiology, and the appropriateness of treatment of these secondary infections has not generally been included in these reports,” added Dr. Bowton, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C.

One such early retrospective cohort study included 191 COVID-19 patients in Wuhan, China. Of the 54 who died in hospital, half had secondary bacterial lung infections (Lancet. 2020 Mar 28;395[10229]:1054-62). That comes as no surprise to U.S. pulmonologists, who learned back in their training that many deaths during the so-called Spanish influenza epidemic of 1918-1920 were actually caused by secondary pneumonia involving Staphylococcus aureus, commented Daniel L. Ouellette, MD, FCCP, associate director of medical critical care at Henry Ford Hospital, Detroit.

“Critically ill patients are highly susceptible to secondary infections regardless of the cause of the patient’s critical illness,” he noted in an interview. “Recent reports of secondary infections in patients critically ill from COVID-19 are interesting but should be considered in this context. To confirm that COVID-19 patients have a different, or increased, risk of infection at specific sites or from specific agents will require careful study.”

That will be no easy matter given the challenges of obtaining bronchoalveolar lavage samples in mechanically ventilated patients with COVID-19, according to Eric J. Gartman, MD, FCCP, a pulmonologist at Brown University, Providence, R.I., and director of the pulmonary function laboratory at the Providence Veterans Affairs Medical Center.

“Unfortunately, many of the invasive modalities that are typically employed to help diagnose secondary infections in critically ill patients are being severely limited or even prohibited in COVID-19 patients due to infection control measures,” he said. As a result, Dr. Gartman noted, intensivists are often resorting to empiric broad-spectrum antimicrobial therapy in patients with severe COVID-19 and are without ready access to the bacterial cultures which might otherwise permit later treatment de-escalation or retargeting.

Among the myriad areas of uncertainty regarding COVID-19 is the proportion of bacterial coinfections that are hospital acquired. Given the lengthy duration of invasive mechanical ventilation in patients with severe COVID-19 – a mean of 9.1 days in the United Kingdom – the chances of hospital-acquired infection are likely substantial. Moreover, a recent single-center U.K. study involving microbiologic testing in 195 consecutive patients newly hospitalized for COVID-19 reported that community-acquired bacterial infection was uncommon: Just 4% of patients had pneumococcal coinfection at hospital admission, and S. aureus wasn’t detected in anyone (Lancet. 2020;1:362. doi:10.1016/S2666-5247[20]30036-7). French investigators have reported detecting putative invasive pulmonary aspergillosis in nearly one-third of a small series of 27 consecutive mechanically ventilated COVID-19 patients (Lancet Resp Med. 2020; 8[6]:e48-9). Dr. Gartman said the diagnostic testing methods utilized in this and similar reports haven’t been prospectively validated in COVID-19. The testing methods may not indicate invasive Aspergillus infection in this population with a high degree of certainty, since they have previously been performed mainly in patients with hematologic malignancies.

“Although there is nothing definitive regarding this research, as a practicing critical care doctor one should respect these findings and consider this secondary diagnosis if the supporting clinical data is positive, especially given that the mortality risk in this population is high,” he advised.

Dr. Bowton said that he and his fellow intensivists at Wake Forest Baptist Health don’t routinely screen COVID-19 patients for secondary bacterial or fungal infections. And in talking with colleagues around the country, it’s his impression that most have similarly elected not to do so.

“However, our clinical index of suspicion for secondary infections is heightened and, if triggered, will initiate a search for and treatment of these secondary infections,” Dr. Bowton said.
 

bjancin@mdedge.com

Secondary respiratory infections appear to be highly prevalent among patients with severe COVID-19, but at this point, most pulmonologists aren’t sure what to make of this understudied phenomenon.

“We really do not understand the implications of secondary infections on outcomes in COVID-19 patients,” David L. Bowton, MD, FCCP, said in an interview. “In most early reports the incidence of secondary infections was much higher in patients dying from COVID-19, compared to survivors, but it isn’t clear whether this indicates that the secondary infection itself led to excess mortality or was more a marker of the severity of the COVID-19 infection.

“Further, details of the diagnostic criteria used, the microbiology, and the appropriateness of treatment of these secondary infections has not generally been included in these reports,” added Dr. Bowton, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C.

One such early retrospective cohort study included 191 COVID-19 patients in Wuhan, China. Of the 54 who died in hospital, half had secondary bacterial lung infections (Lancet. 2020 Mar 28;395[10229]:1054-62). That comes as no surprise to U.S. pulmonologists, who learned back in their training that many deaths during the so-called Spanish influenza epidemic of 1918-1920 were actually caused by secondary pneumonia involving Staphylococcus aureus, commented Daniel L. Ouellette, MD, FCCP, associate director of medical critical care at Henry Ford Hospital, Detroit.

“Critically ill patients are highly susceptible to secondary infections regardless of the cause of the patient’s critical illness,” he noted in an interview. “Recent reports of secondary infections in patients critically ill from COVID-19 are interesting but should be considered in this context. To confirm that COVID-19 patients have a different, or increased, risk of infection at specific sites or from specific agents will require careful study.”

That will be no easy matter given the challenges of obtaining bronchoalveolar lavage samples in mechanically ventilated patients with COVID-19, according to Eric J. Gartman, MD, FCCP, a pulmonologist at Brown University, Providence, R.I., and director of the pulmonary function laboratory at the Providence Veterans Affairs Medical Center.

“Unfortunately, many of the invasive modalities that are typically employed to help diagnose secondary infections in critically ill patients are being severely limited or even prohibited in COVID-19 patients due to infection control measures,” he said. As a result, Dr. Gartman noted, intensivists are often resorting to empiric broad-spectrum antimicrobial therapy in patients with severe COVID-19 and are without ready access to the bacterial cultures which might otherwise permit later treatment de-escalation or retargeting.

Among the myriad areas of uncertainty regarding COVID-19 is the proportion of bacterial coinfections that are hospital acquired. Given the lengthy duration of invasive mechanical ventilation in patients with severe COVID-19 – a mean of 9.1 days in the United Kingdom – the chances of hospital-acquired infection are likely substantial. Moreover, a recent single-center U.K. study involving microbiologic testing in 195 consecutive patients newly hospitalized for COVID-19 reported that community-acquired bacterial infection was uncommon: Just 4% of patients had pneumococcal coinfection at hospital admission, and S. aureus wasn’t detected in anyone (Lancet. 2020;1:362. doi:10.1016/S2666-5247[20]30036-7). French investigators have reported detecting putative invasive pulmonary aspergillosis in nearly one-third of a small series of 27 consecutive mechanically ventilated COVID-19 patients (Lancet Resp Med. 2020; 8[6]:e48-9). Dr. Gartman said the diagnostic testing methods utilized in this and similar reports haven’t been prospectively validated in COVID-19. The testing methods may not indicate invasive Aspergillus infection in this population with a high degree of certainty, since they have previously been performed mainly in patients with hematologic malignancies.

“Although there is nothing definitive regarding this research, as a practicing critical care doctor one should respect these findings and consider this secondary diagnosis if the supporting clinical data is positive, especially given that the mortality risk in this population is high,” he advised.

Dr. Bowton said that he and his fellow intensivists at Wake Forest Baptist Health don’t routinely screen COVID-19 patients for secondary bacterial or fungal infections. And in talking with colleagues around the country, it’s his impression that most have similarly elected not to do so.

“However, our clinical index of suspicion for secondary infections is heightened and, if triggered, will initiate a search for and treatment of these secondary infections,” Dr. Bowton said.
 

bjancin@mdedge.com

Secondary respiratory infections appear to be highly prevalent among patients with severe COVID-19, but at this point, most pulmonologists aren’t sure what to make of this understudied phenomenon.

“We really do not understand the implications of secondary infections on outcomes in COVID-19 patients,” David L. Bowton, MD, FCCP, said in an interview. “In most early reports the incidence of secondary infections was much higher in patients dying from COVID-19, compared to survivors, but it isn’t clear whether this indicates that the secondary infection itself led to excess mortality or was more a marker of the severity of the COVID-19 infection.

“Further, details of the diagnostic criteria used, the microbiology, and the appropriateness of treatment of these secondary infections has not generally been included in these reports,” added Dr. Bowton, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C.

One such early retrospective cohort study included 191 COVID-19 patients in Wuhan, China. Of the 54 who died in hospital, half had secondary bacterial lung infections (Lancet. 2020 Mar 28;395[10229]:1054-62). That comes as no surprise to U.S. pulmonologists, who learned back in their training that many deaths during the so-called Spanish influenza epidemic of 1918-1920 were actually caused by secondary pneumonia involving Staphylococcus aureus, commented Daniel L. Ouellette, MD, FCCP, associate director of medical critical care at Henry Ford Hospital, Detroit.

“Critically ill patients are highly susceptible to secondary infections regardless of the cause of the patient’s critical illness,” he noted in an interview. “Recent reports of secondary infections in patients critically ill from COVID-19 are interesting but should be considered in this context. To confirm that COVID-19 patients have a different, or increased, risk of infection at specific sites or from specific agents will require careful study.”

That will be no easy matter given the challenges of obtaining bronchoalveolar lavage samples in mechanically ventilated patients with COVID-19, according to Eric J. Gartman, MD, FCCP, a pulmonologist at Brown University, Providence, R.I., and director of the pulmonary function laboratory at the Providence Veterans Affairs Medical Center.

“Unfortunately, many of the invasive modalities that are typically employed to help diagnose secondary infections in critically ill patients are being severely limited or even prohibited in COVID-19 patients due to infection control measures,” he said. As a result, Dr. Gartman noted, intensivists are often resorting to empiric broad-spectrum antimicrobial therapy in patients with severe COVID-19 and are without ready access to the bacterial cultures which might otherwise permit later treatment de-escalation or retargeting.

Among the myriad areas of uncertainty regarding COVID-19 is the proportion of bacterial coinfections that are hospital acquired. Given the lengthy duration of invasive mechanical ventilation in patients with severe COVID-19 – a mean of 9.1 days in the United Kingdom – the chances of hospital-acquired infection are likely substantial. Moreover, a recent single-center U.K. study involving microbiologic testing in 195 consecutive patients newly hospitalized for COVID-19 reported that community-acquired bacterial infection was uncommon: Just 4% of patients had pneumococcal coinfection at hospital admission, and S. aureus wasn’t detected in anyone (Lancet. 2020;1:362. doi:10.1016/S2666-5247[20]30036-7). French investigators have reported detecting putative invasive pulmonary aspergillosis in nearly one-third of a small series of 27 consecutive mechanically ventilated COVID-19 patients (Lancet Resp Med. 2020; 8[6]:e48-9). Dr. Gartman said the diagnostic testing methods utilized in this and similar reports haven’t been prospectively validated in COVID-19. The testing methods may not indicate invasive Aspergillus infection in this population with a high degree of certainty, since they have previously been performed mainly in patients with hematologic malignancies.

“Although there is nothing definitive regarding this research, as a practicing critical care doctor one should respect these findings and consider this secondary diagnosis if the supporting clinical data is positive, especially given that the mortality risk in this population is high,” he advised.

Dr. Bowton said that he and his fellow intensivists at Wake Forest Baptist Health don’t routinely screen COVID-19 patients for secondary bacterial or fungal infections. And in talking with colleagues around the country, it’s his impression that most have similarly elected not to do so.

“However, our clinical index of suspicion for secondary infections is heightened and, if triggered, will initiate a search for and treatment of these secondary infections,” Dr. Bowton said.
 

bjancin@mdedge.com

Exposure to Shiga toxin induces a complex intestinal response involving transcriptional changes, necrosis, apoptotic cell death, cellular proliferation, and cross-talk between epithelial and mesenchymal cells, according to investigators.

The study explored new territory in Shiga toxin research, enabled by the use of human intestinal organoids (HIOs), reported lead author Suman Pradhan, PhD, of the University of Cincinnati, and colleagues.

Each year, Shiga toxin–producing Escherichia coli infections cause approximately 3 million cases of bloody diarrheal disease, with about 4,000 of those patients developing the life-threatening complication of hemolytic uremic syndrome (HUS), the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.

But little is known about the underlying biological processes driving Shiga-induced disease.

“Developing effective interventions for disease resulting from Shiga toxin is exacerbated by a lack of tractable model systems,” the investigators wrote. “Mice do not develop the symptoms characteristic of HUS, and the murine intestinal tract is resistant to Shiga toxin.”

To overcome this obstacle, Dr. Pradhan and colleagues turned to HIOs, which are grown in culture by directing differentiation of pluripotent stem cells. HIOs represent the small bowel, complete with a lumen surrounded by epithelial and mesenchymal layers that include typical cell types, such as goblet cells and myofibroblasts. The model is made more realistic by transplantation into mice, where it grows under the kidney capsule to form crypts, structured villi, and proliferating progenitor zones. And HIOs grown with neuronal precursors develop an enteric nervous system, complete with functional peristalsis.

For the present study, the investigators evaluated the effect of Shiga toxin on HIOs both in culture and after transplantation into mice.

First, they demonstrated that HIOs in culture expressed glycolipid Gb3, the Shiga toxin receptor. “Reports regarding expression of glycolipid Gb3 ... on human intestine have been inconsistent,” the investigators noted. “For negative reports, the inability to detect Gb3 could be owing to technical limitations.”

Next, Dr. Pradhan and colleagues showed that HIOs were susceptible to Shiga toxin whether it be delivered lumenally or basolaterally, which respectively represent intestinal exposure and exposure via circulating toxin or after breakdown of the epithelial barrier. Leakage from the lumen was observed with both Shiga toxin 1 (Stx1) and 2 (Stx2). Subsequent testing involved only Stx2, as this form is more relevant to human disease.

In addition to lumenal leakage, Stx2 exposure caused significant transcriptional up-regulation of multiple gene families, including those involved in cellular transport and metabolic processes. Increased expression also was observed for epithelial structural proteins, lineage-specific proteins, factors involved in mucus layer formation and stabilization, and cytokines interleukin-18 and CCL15.

In both epithelial and mesenchymal layers, transcriptional changes were accompanied by cellular necrosis and apoptosis, and, to a greater degree with interstitial exposure, cellular proliferation.

With lumenal exposure, mesenchymal necrosis was observed before loss of epithelial barrier function, indicating toxin access to mesenchymal cells. This phenomenon was explained by transcytosis, which the investigators observed in two-dimensional monolayers of enteroids grown in Transwells.

“[Shiga toxin] was transferred from the apical to the basolateral surface in the absence of loss of epithelial barrier function,” the investigators wrote, noting that this finding explains how Shiga toxin can quickly access the circulatory system, and from there damage the kidneys and brain, as seen in cases of HUS.

Mice with transplanted HIOs, and those receiving HIOs with an enteric nervous system (HIO + ENS), lost weight when organoids were injected with 10 ng of Stx2. Mice with HIO + ENS transplants developed more severe responses, prompting closer analysis.

Postmortem histologic examination of HIO + ENS transplants revealed epithelial damage and blood accumulation in the mesenchyme and villi. Additional staining showed signs of apoptosis and mesenchymal-epithelial transition.

Dr. Pradham and colleagues suggested that their findings could inform therapeutic research.

“If preventing cellular death is to be an effective intervention, it is likely that both necrosis and apoptosis need to be targeted,” the investigators wrote.

More generally, the study supports the use of HIOs as a disease model for future investigations.

“The advent of stem cell–derived human tissue models, both in vitro and in vivo, has a tremendous potential to increase our understanding of Shiga toxin disease and lead to development of therapeutic interventions,” the investigators concluded.

The study was funded by the National Institutes of Health, the Center for Clinical and Translational Science, the National Institute of Diabetes and Digestive and Kidney Diseases, and others. The investigators disclosed no conflicts of interest.

SOURCE: Pradhan S et al. Cell Mol Gastroenterol Hepatol. 2020 Mar 5. doi: 10.1016/j.jcmgh.2020.02.006.

Exposure to Shiga toxin induces a complex intestinal response involving transcriptional changes, necrosis, apoptotic cell death, cellular proliferation, and cross-talk between epithelial and mesenchymal cells, according to investigators.

The study explored new territory in Shiga toxin research, enabled by the use of human intestinal organoids (HIOs), reported lead author Suman Pradhan, PhD, of the University of Cincinnati, and colleagues.

Each year, Shiga toxin–producing Escherichia coli infections cause approximately 3 million cases of bloody diarrheal disease, with about 4,000 of those patients developing the life-threatening complication of hemolytic uremic syndrome (HUS), the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.

But little is known about the underlying biological processes driving Shiga-induced disease.

“Developing effective interventions for disease resulting from Shiga toxin is exacerbated by a lack of tractable model systems,” the investigators wrote. “Mice do not develop the symptoms characteristic of HUS, and the murine intestinal tract is resistant to Shiga toxin.”

To overcome this obstacle, Dr. Pradhan and colleagues turned to HIOs, which are grown in culture by directing differentiation of pluripotent stem cells. HIOs represent the small bowel, complete with a lumen surrounded by epithelial and mesenchymal layers that include typical cell types, such as goblet cells and myofibroblasts. The model is made more realistic by transplantation into mice, where it grows under the kidney capsule to form crypts, structured villi, and proliferating progenitor zones. And HIOs grown with neuronal precursors develop an enteric nervous system, complete with functional peristalsis.

For the present study, the investigators evaluated the effect of Shiga toxin on HIOs both in culture and after transplantation into mice.

First, they demonstrated that HIOs in culture expressed glycolipid Gb3, the Shiga toxin receptor. “Reports regarding expression of glycolipid Gb3 ... on human intestine have been inconsistent,” the investigators noted. “For negative reports, the inability to detect Gb3 could be owing to technical limitations.”

Next, Dr. Pradhan and colleagues showed that HIOs were susceptible to Shiga toxin whether it be delivered lumenally or basolaterally, which respectively represent intestinal exposure and exposure via circulating toxin or after breakdown of the epithelial barrier. Leakage from the lumen was observed with both Shiga toxin 1 (Stx1) and 2 (Stx2). Subsequent testing involved only Stx2, as this form is more relevant to human disease.

In addition to lumenal leakage, Stx2 exposure caused significant transcriptional up-regulation of multiple gene families, including those involved in cellular transport and metabolic processes. Increased expression also was observed for epithelial structural proteins, lineage-specific proteins, factors involved in mucus layer formation and stabilization, and cytokines interleukin-18 and CCL15.

In both epithelial and mesenchymal layers, transcriptional changes were accompanied by cellular necrosis and apoptosis, and, to a greater degree with interstitial exposure, cellular proliferation.

With lumenal exposure, mesenchymal necrosis was observed before loss of epithelial barrier function, indicating toxin access to mesenchymal cells. This phenomenon was explained by transcytosis, which the investigators observed in two-dimensional monolayers of enteroids grown in Transwells.

“[Shiga toxin] was transferred from the apical to the basolateral surface in the absence of loss of epithelial barrier function,” the investigators wrote, noting that this finding explains how Shiga toxin can quickly access the circulatory system, and from there damage the kidneys and brain, as seen in cases of HUS.

Mice with transplanted HIOs, and those receiving HIOs with an enteric nervous system (HIO + ENS), lost weight when organoids were injected with 10 ng of Stx2. Mice with HIO + ENS transplants developed more severe responses, prompting closer analysis.

Postmortem histologic examination of HIO + ENS transplants revealed epithelial damage and blood accumulation in the mesenchyme and villi. Additional staining showed signs of apoptosis and mesenchymal-epithelial transition.

Dr. Pradham and colleagues suggested that their findings could inform therapeutic research.

“If preventing cellular death is to be an effective intervention, it is likely that both necrosis and apoptosis need to be targeted,” the investigators wrote.

More generally, the study supports the use of HIOs as a disease model for future investigations.

“The advent of stem cell–derived human tissue models, both in vitro and in vivo, has a tremendous potential to increase our understanding of Shiga toxin disease and lead to development of therapeutic interventions,” the investigators concluded.

The study was funded by the National Institutes of Health, the Center for Clinical and Translational Science, the National Institute of Diabetes and Digestive and Kidney Diseases, and others. The investigators disclosed no conflicts of interest.

SOURCE: Pradhan S et al. Cell Mol Gastroenterol Hepatol. 2020 Mar 5. doi: 10.1016/j.jcmgh.2020.02.006.

Exposure to Shiga toxin induces a complex intestinal response involving transcriptional changes, necrosis, apoptotic cell death, cellular proliferation, and cross-talk between epithelial and mesenchymal cells, according to investigators.

The study explored new territory in Shiga toxin research, enabled by the use of human intestinal organoids (HIOs), reported lead author Suman Pradhan, PhD, of the University of Cincinnati, and colleagues.

Each year, Shiga toxin–producing Escherichia coli infections cause approximately 3 million cases of bloody diarrheal disease, with about 4,000 of those patients developing the life-threatening complication of hemolytic uremic syndrome (HUS), the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.

But little is known about the underlying biological processes driving Shiga-induced disease.

“Developing effective interventions for disease resulting from Shiga toxin is exacerbated by a lack of tractable model systems,” the investigators wrote. “Mice do not develop the symptoms characteristic of HUS, and the murine intestinal tract is resistant to Shiga toxin.”

To overcome this obstacle, Dr. Pradhan and colleagues turned to HIOs, which are grown in culture by directing differentiation of pluripotent stem cells. HIOs represent the small bowel, complete with a lumen surrounded by epithelial and mesenchymal layers that include typical cell types, such as goblet cells and myofibroblasts. The model is made more realistic by transplantation into mice, where it grows under the kidney capsule to form crypts, structured villi, and proliferating progenitor zones. And HIOs grown with neuronal precursors develop an enteric nervous system, complete with functional peristalsis.

For the present study, the investigators evaluated the effect of Shiga toxin on HIOs both in culture and after transplantation into mice.

First, they demonstrated that HIOs in culture expressed glycolipid Gb3, the Shiga toxin receptor. “Reports regarding expression of glycolipid Gb3 ... on human intestine have been inconsistent,” the investigators noted. “For negative reports, the inability to detect Gb3 could be owing to technical limitations.”

Next, Dr. Pradhan and colleagues showed that HIOs were susceptible to Shiga toxin whether it be delivered lumenally or basolaterally, which respectively represent intestinal exposure and exposure via circulating toxin or after breakdown of the epithelial barrier. Leakage from the lumen was observed with both Shiga toxin 1 (Stx1) and 2 (Stx2). Subsequent testing involved only Stx2, as this form is more relevant to human disease.

In addition to lumenal leakage, Stx2 exposure caused significant transcriptional up-regulation of multiple gene families, including those involved in cellular transport and metabolic processes. Increased expression also was observed for epithelial structural proteins, lineage-specific proteins, factors involved in mucus layer formation and stabilization, and cytokines interleukin-18 and CCL15.

In both epithelial and mesenchymal layers, transcriptional changes were accompanied by cellular necrosis and apoptosis, and, to a greater degree with interstitial exposure, cellular proliferation.

With lumenal exposure, mesenchymal necrosis was observed before loss of epithelial barrier function, indicating toxin access to mesenchymal cells. This phenomenon was explained by transcytosis, which the investigators observed in two-dimensional monolayers of enteroids grown in Transwells.

“[Shiga toxin] was transferred from the apical to the basolateral surface in the absence of loss of epithelial barrier function,” the investigators wrote, noting that this finding explains how Shiga toxin can quickly access the circulatory system, and from there damage the kidneys and brain, as seen in cases of HUS.

Mice with transplanted HIOs, and those receiving HIOs with an enteric nervous system (HIO + ENS), lost weight when organoids were injected with 10 ng of Stx2. Mice with HIO + ENS transplants developed more severe responses, prompting closer analysis.

Postmortem histologic examination of HIO + ENS transplants revealed epithelial damage and blood accumulation in the mesenchyme and villi. Additional staining showed signs of apoptosis and mesenchymal-epithelial transition.

Dr. Pradham and colleagues suggested that their findings could inform therapeutic research.

“If preventing cellular death is to be an effective intervention, it is likely that both necrosis and apoptosis need to be targeted,” the investigators wrote.

More generally, the study supports the use of HIOs as a disease model for future investigations.

“The advent of stem cell–derived human tissue models, both in vitro and in vivo, has a tremendous potential to increase our understanding of Shiga toxin disease and lead to development of therapeutic interventions,” the investigators concluded.

The study was funded by the National Institutes of Health, the Center for Clinical and Translational Science, the National Institute of Diabetes and Digestive and Kidney Diseases, and others. The investigators disclosed no conflicts of interest.

SOURCE: Pradhan S et al. Cell Mol Gastroenterol Hepatol. 2020 Mar 5. doi: 10.1016/j.jcmgh.2020.02.006.

Although it is not glamorous, snail mucus is a popular ingredient in skin care products. Its use dates back to ancient Greece, where Hippocrates reportedly applied crushed snails to treat skin inflammations.¹ The modern consideration of using snail secretions in skin care arose serendipitously in the 1990s when Chilean farmers observed accelerated healing of their skin lesions without scarring after handling snails.¹

valentinrussanov/E+

Today, snail mucin is among the increasingly wide array of bioactive ingredients undergoing scientific validation and inclusion in the burgeoning Korean cosmeceutical market.^2,3 In fact, a variety of Korean cosmeceuticals incorporate the mucus derived from Achatina fulica (African giant land snail) and Cryptomphalus (Helix) aspersa (common brown garden snail) based on their demonstrated antimicrobial and skin regenerative activity.^1,3,4 The antioxidant properties also attributed to snail mucus are thought to originate in constituents such as glycosaminoglycans, as well as growth factors, and may justify the use of these ingredients in novel cosmeceuticals.⁵ The focus of this discussion is recent research into the novel use of this animal-derived product for dermatologic purposes.
 

Antioxidant activity, skin rejuvenation, and wound healing

In 2008, Brieva et al. reported on a screen for natural products yielding a molecular basis for the secretions of the mollusk Cryptomphalus aspersa, which displays skin-regenerative activity. Specifically, they found that the secretion exerts antioxidant superoxide dismutase and glutathione S-transferase, and spurred fibroblast proliferation and extracellular matrix assembly while regulating metalloproteinase function. The researchers concluded that such activities may support wound regeneration.⁵

Four years later, Cruz et al. found that secretions of C. aspersa promote in vitro cell proliferation and migration by localizing beta-catenin to the nuclei of human fibroblasts and keratinocytes, augment phosphorylated focal adhesion kinase, and thereby enhance cell survival. The investigators concluded that snail secretions may therefore impart regenerative and wound healing activity.3,6

Antimicrobial properties

In 2015, Pitt et al. investigated the antimicrobial properties of the mucus of the brown garden snail C. or H. aspersa, which had a reputation for exhibiting skin regeneration capabilities. Their results revealed that snail mucus displayed a strong antibacterial effect against multiple strains of Pseudomonas aeruginosa and a weak effect against Staphylococcus aureus.⁴

Indications for the use of snail mucin

Radiation-induced dermatitis and burns represented the first indication for the initial use of snail mucin as a cutaneous therapy.⁷ Experimental and clinical studies have since been performed to assess its applicability to treat acute radiation dermatitis, atopic dermatitis, partial-thickness burns, and photoaging.^8-11

A 2017 in vitro investigation by Ellijimi et al. revealed that snail mucin displayed antimelanogenic and antitumoral activity against human melanoma cells, suggesting another possible application of this product.¹²

Human studies on photoaging

In a 2009 study by Tsoutsos et al. of an open, moist burn management protocol in deep partial-thickness facial burns, a cream containing H. aspersa secretions was identified to be an effective treatment option. For 14 days or until full epithelialization, 27 adult patients were treated with snail extract cream twice daily. Comparisons were made to 16 patients treated with moist exposure burn ointment. Visual analog scale pain scores were significantly lower in the group that received the H. aspersa cream, compared with the moist exposure burn group. The researchers concluded that the H. aspersa cream is a safe, effective, and natural option for treating partial-thickness burns in adults that acts by facilitating debris removal and accelerating reepithelialization.¹⁰

Also that year, Tribo-Boixareu et al. treated 15 patients with chronic photodamage with secretions of C. aspersa over a 3-month period, yielding significant amelioration in the clinical and histologic markers of photoaging.¹¹

Four years later, a double-blind, split-face, randomized, controlled clinical study conducted by Fabi et al. over 12 weeks demonstrated that the topical application of an antiphotoaging formulation containing C. aspersa mucus diminished periocular and fine facial rhytides and enhanced skin texture within 8 weeks of treatment initiation.⁷

Snail eggs and photoaging

In 2015, Espada et al. determined in vitro that an extract derived from C. aspersa eggs could reorganize the cytoskeleton of keratinocytes and fibroblasts, as well as trigger the synthesis of the extracellular proteins collagen and fibronectin. They also found that gene expression declined in age-related genes including p53 and b-Gal. The researchers concluded that C. aspersa egg extract has the potential to reduce the signs of photoaging.^3,13

Antiaging cosmeceuticals

In a 2017 assessment of the antiaging and skin-whitening activity of the nine most popular ingredients in the South Korean skin care product market, Quay et al. considered industry profit data from Euromonitor and conducted a comprehensive literature search. They identified licorice, niacinamide, green tea, soy, beta-glucan, snail mucus, ginkgo biloba, ginseng, and pomegranate as the nine most popular ingredients, with the first four associated with the most supportive data. They found a paucity of cogent evidence on the use of the other ingredients in antiaging and skin-whitening formulations.¹⁴

Conclusion

The use of snail mucin to treat skin dates back at least to the time of Hippocrates. Recent research suggests reasons for optimism, and further investigation, as this ingredient appears to have potential across various cutaneous conditions. As is often the case, though, much more research is necessary to ascertain what enduring benefits may be derived from the use of snail mucin. Nevertheless, this product has been available on the market for the last 20 years and is associated with anecdotal reports of efficacy.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at dermnews@mdedge.com. She has no relevant disclosures.

References

1. Liu L et al. Snails and skin care – an uncovered combination. JAMA Dermatol. 2017 Jul 1;153(7):650.

2. Nguyen JK et al. J Cosmet Dermatol. 2020 Feb 26. doi: 10.1111/jocd.13344.

3. Juhász ML et al. J Cosmet Dermatol. 2018;17(3):305-12.

4. Pitt SJ et al. Br J Biomed Sci. 2015;72(4):174-81.

5. Brieva A et al. Skin Pharmacol Physiol. 2008;21(1):15-22.

6. Cruz MC et al. Int J Cosmet Sci. 2012 Apr;34(2):183-9.

7. Fabi SG et al. J Drugs Dermatol. 2013; Apr;12(4):453-7.

8. Ledo E et al. Radioproteccion. 1999;23(7):34-8.

9. Oh M-Jet al. J Korean Med Ophthalmol Otolaryngol Dermatol. 2010; Dec,23(3):138-53.

10. Tsoutsos D et al. J Dermatolog Treat. 2009;20(4):219-22.

11. Tribo-Boixareu MJ et al. Cosmet Dermatol. 2009;22(5):247-52.

12. Ellijimi C et al. Biomed Pharmacother. 2018 May;101:871-80.

13. Espada J et al. Int J Cosmet Sci. 2015 Feb;37(1):41-55.

14. Quay ER et al. J Drugs Dermatol. 2017 Apr 1;16(4):358-63.
 

Although it is not glamorous, snail mucus is a popular ingredient in skin care products. Its use dates back to ancient Greece, where Hippocrates reportedly applied crushed snails to treat skin inflammations.¹ The modern consideration of using snail secretions in skin care arose serendipitously in the 1990s when Chilean farmers observed accelerated healing of their skin lesions without scarring after handling snails.¹

valentinrussanov/E+

Today, snail mucin is among the increasingly wide array of bioactive ingredients undergoing scientific validation and inclusion in the burgeoning Korean cosmeceutical market.^2,3 In fact, a variety of Korean cosmeceuticals incorporate the mucus derived from Achatina fulica (African giant land snail) and Cryptomphalus (Helix) aspersa (common brown garden snail) based on their demonstrated antimicrobial and skin regenerative activity.^1,3,4 The antioxidant properties also attributed to snail mucus are thought to originate in constituents such as glycosaminoglycans, as well as growth factors, and may justify the use of these ingredients in novel cosmeceuticals.⁵ The focus of this discussion is recent research into the novel use of this animal-derived product for dermatologic purposes.
 

Antioxidant activity, skin rejuvenation, and wound healing

In 2008, Brieva et al. reported on a screen for natural products yielding a molecular basis for the secretions of the mollusk Cryptomphalus aspersa, which displays skin-regenerative activity. Specifically, they found that the secretion exerts antioxidant superoxide dismutase and glutathione S-transferase, and spurred fibroblast proliferation and extracellular matrix assembly while regulating metalloproteinase function. The researchers concluded that such activities may support wound regeneration.⁵

Four years later, Cruz et al. found that secretions of C. aspersa promote in vitro cell proliferation and migration by localizing beta-catenin to the nuclei of human fibroblasts and keratinocytes, augment phosphorylated focal adhesion kinase, and thereby enhance cell survival. The investigators concluded that snail secretions may therefore impart regenerative and wound healing activity.3,6

Antimicrobial properties

In 2015, Pitt et al. investigated the antimicrobial properties of the mucus of the brown garden snail C. or H. aspersa, which had a reputation for exhibiting skin regeneration capabilities. Their results revealed that snail mucus displayed a strong antibacterial effect against multiple strains of Pseudomonas aeruginosa and a weak effect against Staphylococcus aureus.⁴

Indications for the use of snail mucin

Radiation-induced dermatitis and burns represented the first indication for the initial use of snail mucin as a cutaneous therapy.⁷ Experimental and clinical studies have since been performed to assess its applicability to treat acute radiation dermatitis, atopic dermatitis, partial-thickness burns, and photoaging.^8-11

A 2017 in vitro investigation by Ellijimi et al. revealed that snail mucin displayed antimelanogenic and antitumoral activity against human melanoma cells, suggesting another possible application of this product.¹²

Human studies on photoaging

In a 2009 study by Tsoutsos et al. of an open, moist burn management protocol in deep partial-thickness facial burns, a cream containing H. aspersa secretions was identified to be an effective treatment option. For 14 days or until full epithelialization, 27 adult patients were treated with snail extract cream twice daily. Comparisons were made to 16 patients treated with moist exposure burn ointment. Visual analog scale pain scores were significantly lower in the group that received the H. aspersa cream, compared with the moist exposure burn group. The researchers concluded that the H. aspersa cream is a safe, effective, and natural option for treating partial-thickness burns in adults that acts by facilitating debris removal and accelerating reepithelialization.¹⁰

Also that year, Tribo-Boixareu et al. treated 15 patients with chronic photodamage with secretions of C. aspersa over a 3-month period, yielding significant amelioration in the clinical and histologic markers of photoaging.¹¹

Four years later, a double-blind, split-face, randomized, controlled clinical study conducted by Fabi et al. over 12 weeks demonstrated that the topical application of an antiphotoaging formulation containing C. aspersa mucus diminished periocular and fine facial rhytides and enhanced skin texture within 8 weeks of treatment initiation.⁷

Snail eggs and photoaging

In 2015, Espada et al. determined in vitro that an extract derived from C. aspersa eggs could reorganize the cytoskeleton of keratinocytes and fibroblasts, as well as trigger the synthesis of the extracellular proteins collagen and fibronectin. They also found that gene expression declined in age-related genes including p53 and b-Gal. The researchers concluded that C. aspersa egg extract has the potential to reduce the signs of photoaging.^3,13

Antiaging cosmeceuticals

In a 2017 assessment of the antiaging and skin-whitening activity of the nine most popular ingredients in the South Korean skin care product market, Quay et al. considered industry profit data from Euromonitor and conducted a comprehensive literature search. They identified licorice, niacinamide, green tea, soy, beta-glucan, snail mucus, ginkgo biloba, ginseng, and pomegranate as the nine most popular ingredients, with the first four associated with the most supportive data. They found a paucity of cogent evidence on the use of the other ingredients in antiaging and skin-whitening formulations.¹⁴

Conclusion

The use of snail mucin to treat skin dates back at least to the time of Hippocrates. Recent research suggests reasons for optimism, and further investigation, as this ingredient appears to have potential across various cutaneous conditions. As is often the case, though, much more research is necessary to ascertain what enduring benefits may be derived from the use of snail mucin. Nevertheless, this product has been available on the market for the last 20 years and is associated with anecdotal reports of efficacy.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at dermnews@mdedge.com. She has no relevant disclosures.

References

1. Liu L et al. Snails and skin care – an uncovered combination. JAMA Dermatol. 2017 Jul 1;153(7):650.

2. Nguyen JK et al. J Cosmet Dermatol. 2020 Feb 26. doi: 10.1111/jocd.13344.

3. Juhász ML et al. J Cosmet Dermatol. 2018;17(3):305-12.

4. Pitt SJ et al. Br J Biomed Sci. 2015;72(4):174-81.

5. Brieva A et al. Skin Pharmacol Physiol. 2008;21(1):15-22.

6. Cruz MC et al. Int J Cosmet Sci. 2012 Apr;34(2):183-9.

7. Fabi SG et al. J Drugs Dermatol. 2013; Apr;12(4):453-7.

8. Ledo E et al. Radioproteccion. 1999;23(7):34-8.

9. Oh M-Jet al. J Korean Med Ophthalmol Otolaryngol Dermatol. 2010; Dec,23(3):138-53.

10. Tsoutsos D et al. J Dermatolog Treat. 2009;20(4):219-22.

11. Tribo-Boixareu MJ et al. Cosmet Dermatol. 2009;22(5):247-52.

12. Ellijimi C et al. Biomed Pharmacother. 2018 May;101:871-80.

13. Espada J et al. Int J Cosmet Sci. 2015 Feb;37(1):41-55.

14. Quay ER et al. J Drugs Dermatol. 2017 Apr 1;16(4):358-63.
 

Although it is not glamorous, snail mucus is a popular ingredient in skin care products. Its use dates back to ancient Greece, where Hippocrates reportedly applied crushed snails to treat skin inflammations.¹ The modern consideration of using snail secretions in skin care arose serendipitously in the 1990s when Chilean farmers observed accelerated healing of their skin lesions without scarring after handling snails.¹

valentinrussanov/E+

Today, snail mucin is among the increasingly wide array of bioactive ingredients undergoing scientific validation and inclusion in the burgeoning Korean cosmeceutical market.^2,3 In fact, a variety of Korean cosmeceuticals incorporate the mucus derived from Achatina fulica (African giant land snail) and Cryptomphalus (Helix) aspersa (common brown garden snail) based on their demonstrated antimicrobial and skin regenerative activity.^1,3,4 The antioxidant properties also attributed to snail mucus are thought to originate in constituents such as glycosaminoglycans, as well as growth factors, and may justify the use of these ingredients in novel cosmeceuticals.⁵ The focus of this discussion is recent research into the novel use of this animal-derived product for dermatologic purposes.
 

Antioxidant activity, skin rejuvenation, and wound healing

In 2008, Brieva et al. reported on a screen for natural products yielding a molecular basis for the secretions of the mollusk Cryptomphalus aspersa, which displays skin-regenerative activity. Specifically, they found that the secretion exerts antioxidant superoxide dismutase and glutathione S-transferase, and spurred fibroblast proliferation and extracellular matrix assembly while regulating metalloproteinase function. The researchers concluded that such activities may support wound regeneration.⁵

Four years later, Cruz et al. found that secretions of C. aspersa promote in vitro cell proliferation and migration by localizing beta-catenin to the nuclei of human fibroblasts and keratinocytes, augment phosphorylated focal adhesion kinase, and thereby enhance cell survival. The investigators concluded that snail secretions may therefore impart regenerative and wound healing activity.3,6

Antimicrobial properties

In 2015, Pitt et al. investigated the antimicrobial properties of the mucus of the brown garden snail C. or H. aspersa, which had a reputation for exhibiting skin regeneration capabilities. Their results revealed that snail mucus displayed a strong antibacterial effect against multiple strains of Pseudomonas aeruginosa and a weak effect against Staphylococcus aureus.⁴

Indications for the use of snail mucin

Radiation-induced dermatitis and burns represented the first indication for the initial use of snail mucin as a cutaneous therapy.⁷ Experimental and clinical studies have since been performed to assess its applicability to treat acute radiation dermatitis, atopic dermatitis, partial-thickness burns, and photoaging.^8-11

A 2017 in vitro investigation by Ellijimi et al. revealed that snail mucin displayed antimelanogenic and antitumoral activity against human melanoma cells, suggesting another possible application of this product.¹²

Human studies on photoaging

In a 2009 study by Tsoutsos et al. of an open, moist burn management protocol in deep partial-thickness facial burns, a cream containing H. aspersa secretions was identified to be an effective treatment option. For 14 days or until full epithelialization, 27 adult patients were treated with snail extract cream twice daily. Comparisons were made to 16 patients treated with moist exposure burn ointment. Visual analog scale pain scores were significantly lower in the group that received the H. aspersa cream, compared with the moist exposure burn group. The researchers concluded that the H. aspersa cream is a safe, effective, and natural option for treating partial-thickness burns in adults that acts by facilitating debris removal and accelerating reepithelialization.¹⁰

Also that year, Tribo-Boixareu et al. treated 15 patients with chronic photodamage with secretions of C. aspersa over a 3-month period, yielding significant amelioration in the clinical and histologic markers of photoaging.¹¹

Four years later, a double-blind, split-face, randomized, controlled clinical study conducted by Fabi et al. over 12 weeks demonstrated that the topical application of an antiphotoaging formulation containing C. aspersa mucus diminished periocular and fine facial rhytides and enhanced skin texture within 8 weeks of treatment initiation.⁷

Snail eggs and photoaging

In 2015, Espada et al. determined in vitro that an extract derived from C. aspersa eggs could reorganize the cytoskeleton of keratinocytes and fibroblasts, as well as trigger the synthesis of the extracellular proteins collagen and fibronectin. They also found that gene expression declined in age-related genes including p53 and b-Gal. The researchers concluded that C. aspersa egg extract has the potential to reduce the signs of photoaging.^3,13

Antiaging cosmeceuticals

In a 2017 assessment of the antiaging and skin-whitening activity of the nine most popular ingredients in the South Korean skin care product market, Quay et al. considered industry profit data from Euromonitor and conducted a comprehensive literature search. They identified licorice, niacinamide, green tea, soy, beta-glucan, snail mucus, ginkgo biloba, ginseng, and pomegranate as the nine most popular ingredients, with the first four associated with the most supportive data. They found a paucity of cogent evidence on the use of the other ingredients in antiaging and skin-whitening formulations.¹⁴

Conclusion

The use of snail mucin to treat skin dates back at least to the time of Hippocrates. Recent research suggests reasons for optimism, and further investigation, as this ingredient appears to have potential across various cutaneous conditions. As is often the case, though, much more research is necessary to ascertain what enduring benefits may be derived from the use of snail mucin. Nevertheless, this product has been available on the market for the last 20 years and is associated with anecdotal reports of efficacy.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014), and a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. Write to her at dermnews@mdedge.com. She has no relevant disclosures.

References

1. Liu L et al. Snails and skin care – an uncovered combination. JAMA Dermatol. 2017 Jul 1;153(7):650.

2. Nguyen JK et al. J Cosmet Dermatol. 2020 Feb 26. doi: 10.1111/jocd.13344.

3. Juhász ML et al. J Cosmet Dermatol. 2018;17(3):305-12.

4. Pitt SJ et al. Br J Biomed Sci. 2015;72(4):174-81.

5. Brieva A et al. Skin Pharmacol Physiol. 2008;21(1):15-22.

6. Cruz MC et al. Int J Cosmet Sci. 2012 Apr;34(2):183-9.

7. Fabi SG et al. J Drugs Dermatol. 2013; Apr;12(4):453-7.

8. Ledo E et al. Radioproteccion. 1999;23(7):34-8.

9. Oh M-Jet al. J Korean Med Ophthalmol Otolaryngol Dermatol. 2010; Dec,23(3):138-53.

10. Tsoutsos D et al. J Dermatolog Treat. 2009;20(4):219-22.

11. Tribo-Boixareu MJ et al. Cosmet Dermatol. 2009;22(5):247-52.

12. Ellijimi C et al. Biomed Pharmacother. 2018 May;101:871-80.

13. Espada J et al. Int J Cosmet Sci. 2015 Feb;37(1):41-55.

14. Quay ER et al. J Drugs Dermatol. 2017 Apr 1;16(4):358-63.
 

The Abbott FreeStyle Libre glucose monitoring system significantly reduced hospitalizations for diabetic ketoacidosis (DKA), diabetes-related emergencies, and all-cause hospitalizations among patients with diabetes, data from two new studies indicate.

The results were presented June 13 during the virtual American Diabetes Association (ADA) 80th Scientific Sessions.

One large database analysis, from France, revealed that use of the Libre system halved hospitalization rates for DKA among people with type 1 or type 2 diabetes.

In the other study, a retrospective analysis of data from over 1200 insulin-treated individuals with type 2 diabetes in the United States, use of the Libre was associated with significant reductions in both hospitalizations for acute diabetes-related emergency events and all-cause hospitalizations.

The Libre system reads glucose levels through a sensor worn on the back of the upper arm for up to 14 days. Users wave a scanner over the device to obtain a reading.

Asked to comment, Nicholas Argento, MD, diabetes technology director at Maryland Endocrine and Diabetes, Columbia, told Medscape Medical News: “One of the biggest problems with access to continuous glucose monitoring is cost. Payers need to see that there’s some cost-saving to offset the cost of paying for these devices. I think both of these studies are important for that reason.”

However, Argento also said he recommends that people with type 1 diabetes use the Dexcom continuous glucose monitor (CGM) if possible rather than the Libre, despite the former’s higher cost, because it has an alarm feature that the Libre doesn’t and is more accurate in the hypoglycemic range.

Large French study: Libre cuts DKA hospitalizations by 50%

The FreeStyle Libre system has been reimbursed in France since June 1, 2017 for patients over 4 years of age with type 1 or type 2 diabetes who take at least 3 insulin injections per day or use an insulin pump.

Sara Freeman/MDedge News

The new results were presented by Ronan Roussel, MD, PhD, chief of the endocrinology, diabetes, and nutrition department at Hôpital Bichat, Fédération de Diabétologie, AP-HP, Paris, France.

The DKA hospitalization data Roussel reported were part of a larger longitudinal retrospective cohort study looking at overall prescribing and use of the Libre system, and its impact on healthcare outcomes and associated costs in standard practice in France. The data came from a large nationwide claims database containing all healthcare expenses for over 66 million people.

The current study participants were 74,076 individuals with at least a full year of follow-up beginning in 2017 with the date of first reimbursement for the FreeStyle Libre system. Of those, 44.8% (33,203) had type 1 diabetes and 55.2% (40,955) had type 2 diabetes.

Prior to initiation of Libre use, about a quarter of each group was using 0 fingerstick test strips per day, about 19% of the type 1 diabetes group and 28% of the type 2 diabetes group were using 1-3 strips per day, and about half of both groups were using 4 or more strips per day.

Compared with the year prior to the date of first reimbursement for the Libre, hospitalization rates for DKA during the first year of Libre use fell by 52% in the type 1 diabetes group, from 5.46 to 2.59 per 100 patient-years, and by 47% in the type 2 diabetes group, from 1.70 to 0.90 per 100 patient-years.

The impact of Libre on DKA hospitalizations was most dramatic among those not using any test strips prior to Libre use, with a 60% reduction for the type 1 diabetes group (8.31 to 3.31 per 100 patient-years) and a 51% reduction in the type 2 diabetes group (2.51 to 1.23 per 100 patient-years).

But interestingly, the next-biggest impact was among those who had been using more than 5 test strips per day, with drops of 59% among those with type 1 diabetes (5.55 to 2.26 per 100 patient-years) and 52% in the type 2 diabetes group (1.88 to 0.90 per 100 patient-years).

This finding is important for the United States, Argento said, because some insurers, including Medicare, require that the patient performs at least 4 fingerstick glucose measurements per day to qualify for reimbursement for the Libre or any CGM system.

“I think that speaks to the importance of not requiring that patients first show they’re frequently doing self-blood glucose monitoring before they can get these devices,” he observed.

The large benefit in the high strip use group is interesting too, Argento said. “It’s a different group of people. They’re more engaged in their care...This U-shaped curve they showed is fascinating.”

Reductions in DKA hospitalizations were also similar between patients using insulin pumps and those using multiple daily injections of insulin, Roussel reported.

“It is plausible that use of the FreeStyle Libre system allowed people to detect and limit persistent hyperglycemia, and subsequently ketoacidosis,” Roussel said.

“This analysis has significant implications for patient-centered clinical care in diabetes and also for long-term health economic outcomes in the treatment of diabetes at a national level.”

All-cause hospitalizations drop 30% with Libre in type 2 diabetes

Richard M. Bergenstal, MD, executive director of the International Diabetes Center at Park Nicollet, Minneapolis, Minnesota, presented the US results, obtained from the IBM Watson Health MarketScan, a database of commercial and Medicare supplemental insurance claims for over 30 million Americans.

The study population included 2463 patients with type 2 diabetes using basal-bolus daily insulin injections but who had not previously used Libre or any other CGM, and for whom data were available 6 months prior to and after Libre initiation.

Compared with 6 months prior to Libre use, the number of acute diabetes-related events — including hyperglycemia, hypoglycemia, DKA, hypoglycemic coma, and hyperosmolarity — in the subsequent 6 months dropped by 60%, from 0.180 to 0.072 events per patient-year (P < .001).

Similarly significant reductions were seen between males and females, and among those aged ≥ 50 years or < 50 years.

All-cause hospitalizations also significantly dropped by 33% (P < 0.001), from 0.420 to 0.283 events per patient-year. Among diagnostic codes for the hospitalizations, circulatory system causes remained number one during both time periods, with little change from pre-Libre to during Libre use.

However, “endocrine, nutritional, and metabolism system” codes dropped from the second position pre-Libre (6.4 events/100 patient-years) down to the fifth position (2.6 events/100 patient-years).

And, Bergenstal noted, other major diagnostic categories that also dropped included respiratory (3.5 to 2.1 events/100 patient-years), kidney and urinary tract (3.3 to 1.7 events/100 patient-years), and hepatobiliary system and pancreas (2.4 to 1.4 events/100 patient-years).

“We’re seeing a resurgence of certain types of complications, but all of these were reduced in the 6 months after Libre,” Bergenstal pointed out.

And, pertinent to the current COVID-19 situation, “infectious and parasitic disease and disorders” dropped as well, from 4.8 to 2.8 per 100 patient-years.

Argento commented: “The fact that infections went down speaks to something that is important right now. Hyperglycemia impairs immune function chronically, but also acutely...so patients who become ill and their blood glucose deteriorates rapidly are much more likely to have a poor outcome regardless of infection. There are data for COVID-19 now.”

“These findings provide compelling support for use of [Libre] to improve both clinical outcomes and potentially reduce costs in this patient population,” Bergenstal concluded.

Roussel has reported being on advisory panels for Abbott, AstraZeneca, Diabnext, Eli Lilly, Merck, Mundipharma International, Novo Nordisk, and Sanofi-Aventis. Bergenstal has reported being a consultant for Ascensia Diabetes Care, Johnson & Johnson, and has other relationships with Abbott, Dexcom, Hygieia, Lilly Diabetes, Medtronic, Novo Nordisk, Onduo, Roche Diabetes Care, Sanofi, and UnitedHealth Group. Argento has reported consulting and being on speaker bureaus for Omnipod, Eli Lilly, Novo Nordisk, Dexcom, and Boehringer Ingelheim.

This article first appeared on Medscape.com.
 

The Abbott FreeStyle Libre glucose monitoring system significantly reduced hospitalizations for diabetic ketoacidosis (DKA), diabetes-related emergencies, and all-cause hospitalizations among patients with diabetes, data from two new studies indicate.

The results were presented June 13 during the virtual American Diabetes Association (ADA) 80th Scientific Sessions.

One large database analysis, from France, revealed that use of the Libre system halved hospitalization rates for DKA among people with type 1 or type 2 diabetes.

In the other study, a retrospective analysis of data from over 1200 insulin-treated individuals with type 2 diabetes in the United States, use of the Libre was associated with significant reductions in both hospitalizations for acute diabetes-related emergency events and all-cause hospitalizations.

The Libre system reads glucose levels through a sensor worn on the back of the upper arm for up to 14 days. Users wave a scanner over the device to obtain a reading.

Asked to comment, Nicholas Argento, MD, diabetes technology director at Maryland Endocrine and Diabetes, Columbia, told Medscape Medical News: “One of the biggest problems with access to continuous glucose monitoring is cost. Payers need to see that there’s some cost-saving to offset the cost of paying for these devices. I think both of these studies are important for that reason.”

However, Argento also said he recommends that people with type 1 diabetes use the Dexcom continuous glucose monitor (CGM) if possible rather than the Libre, despite the former’s higher cost, because it has an alarm feature that the Libre doesn’t and is more accurate in the hypoglycemic range.

Large French study: Libre cuts DKA hospitalizations by 50%

The FreeStyle Libre system has been reimbursed in France since June 1, 2017 for patients over 4 years of age with type 1 or type 2 diabetes who take at least 3 insulin injections per day or use an insulin pump.

Sara Freeman/MDedge News

The new results were presented by Ronan Roussel, MD, PhD, chief of the endocrinology, diabetes, and nutrition department at Hôpital Bichat, Fédération de Diabétologie, AP-HP, Paris, France.

The DKA hospitalization data Roussel reported were part of a larger longitudinal retrospective cohort study looking at overall prescribing and use of the Libre system, and its impact on healthcare outcomes and associated costs in standard practice in France. The data came from a large nationwide claims database containing all healthcare expenses for over 66 million people.

The current study participants were 74,076 individuals with at least a full year of follow-up beginning in 2017 with the date of first reimbursement for the FreeStyle Libre system. Of those, 44.8% (33,203) had type 1 diabetes and 55.2% (40,955) had type 2 diabetes.

Prior to initiation of Libre use, about a quarter of each group was using 0 fingerstick test strips per day, about 19% of the type 1 diabetes group and 28% of the type 2 diabetes group were using 1-3 strips per day, and about half of both groups were using 4 or more strips per day.

Compared with the year prior to the date of first reimbursement for the Libre, hospitalization rates for DKA during the first year of Libre use fell by 52% in the type 1 diabetes group, from 5.46 to 2.59 per 100 patient-years, and by 47% in the type 2 diabetes group, from 1.70 to 0.90 per 100 patient-years.

The impact of Libre on DKA hospitalizations was most dramatic among those not using any test strips prior to Libre use, with a 60% reduction for the type 1 diabetes group (8.31 to 3.31 per 100 patient-years) and a 51% reduction in the type 2 diabetes group (2.51 to 1.23 per 100 patient-years).

But interestingly, the next-biggest impact was among those who had been using more than 5 test strips per day, with drops of 59% among those with type 1 diabetes (5.55 to 2.26 per 100 patient-years) and 52% in the type 2 diabetes group (1.88 to 0.90 per 100 patient-years).

This finding is important for the United States, Argento said, because some insurers, including Medicare, require that the patient performs at least 4 fingerstick glucose measurements per day to qualify for reimbursement for the Libre or any CGM system.

“I think that speaks to the importance of not requiring that patients first show they’re frequently doing self-blood glucose monitoring before they can get these devices,” he observed.

The large benefit in the high strip use group is interesting too, Argento said. “It’s a different group of people. They’re more engaged in their care...This U-shaped curve they showed is fascinating.”

Reductions in DKA hospitalizations were also similar between patients using insulin pumps and those using multiple daily injections of insulin, Roussel reported.

“It is plausible that use of the FreeStyle Libre system allowed people to detect and limit persistent hyperglycemia, and subsequently ketoacidosis,” Roussel said.

“This analysis has significant implications for patient-centered clinical care in diabetes and also for long-term health economic outcomes in the treatment of diabetes at a national level.”

All-cause hospitalizations drop 30% with Libre in type 2 diabetes

Richard M. Bergenstal, MD, executive director of the International Diabetes Center at Park Nicollet, Minneapolis, Minnesota, presented the US results, obtained from the IBM Watson Health MarketScan, a database of commercial and Medicare supplemental insurance claims for over 30 million Americans.

The study population included 2463 patients with type 2 diabetes using basal-bolus daily insulin injections but who had not previously used Libre or any other CGM, and for whom data were available 6 months prior to and after Libre initiation.

Compared with 6 months prior to Libre use, the number of acute diabetes-related events — including hyperglycemia, hypoglycemia, DKA, hypoglycemic coma, and hyperosmolarity — in the subsequent 6 months dropped by 60%, from 0.180 to 0.072 events per patient-year (P < .001).

Similarly significant reductions were seen between males and females, and among those aged ≥ 50 years or < 50 years.

All-cause hospitalizations also significantly dropped by 33% (P < 0.001), from 0.420 to 0.283 events per patient-year. Among diagnostic codes for the hospitalizations, circulatory system causes remained number one during both time periods, with little change from pre-Libre to during Libre use.

However, “endocrine, nutritional, and metabolism system” codes dropped from the second position pre-Libre (6.4 events/100 patient-years) down to the fifth position (2.6 events/100 patient-years).

And, Bergenstal noted, other major diagnostic categories that also dropped included respiratory (3.5 to 2.1 events/100 patient-years), kidney and urinary tract (3.3 to 1.7 events/100 patient-years), and hepatobiliary system and pancreas (2.4 to 1.4 events/100 patient-years).

“We’re seeing a resurgence of certain types of complications, but all of these were reduced in the 6 months after Libre,” Bergenstal pointed out.

And, pertinent to the current COVID-19 situation, “infectious and parasitic disease and disorders” dropped as well, from 4.8 to 2.8 per 100 patient-years.

Argento commented: “The fact that infections went down speaks to something that is important right now. Hyperglycemia impairs immune function chronically, but also acutely...so patients who become ill and their blood glucose deteriorates rapidly are much more likely to have a poor outcome regardless of infection. There are data for COVID-19 now.”

“These findings provide compelling support for use of [Libre] to improve both clinical outcomes and potentially reduce costs in this patient population,” Bergenstal concluded.

Roussel has reported being on advisory panels for Abbott, AstraZeneca, Diabnext, Eli Lilly, Merck, Mundipharma International, Novo Nordisk, and Sanofi-Aventis. Bergenstal has reported being a consultant for Ascensia Diabetes Care, Johnson & Johnson, and has other relationships with Abbott, Dexcom, Hygieia, Lilly Diabetes, Medtronic, Novo Nordisk, Onduo, Roche Diabetes Care, Sanofi, and UnitedHealth Group. Argento has reported consulting and being on speaker bureaus for Omnipod, Eli Lilly, Novo Nordisk, Dexcom, and Boehringer Ingelheim.

This article first appeared on Medscape.com.
 

The Abbott FreeStyle Libre glucose monitoring system significantly reduced hospitalizations for diabetic ketoacidosis (DKA), diabetes-related emergencies, and all-cause hospitalizations among patients with diabetes, data from two new studies indicate.

The results were presented June 13 during the virtual American Diabetes Association (ADA) 80th Scientific Sessions.

One large database analysis, from France, revealed that use of the Libre system halved hospitalization rates for DKA among people with type 1 or type 2 diabetes.

In the other study, a retrospective analysis of data from over 1200 insulin-treated individuals with type 2 diabetes in the United States, use of the Libre was associated with significant reductions in both hospitalizations for acute diabetes-related emergency events and all-cause hospitalizations.

The Libre system reads glucose levels through a sensor worn on the back of the upper arm for up to 14 days. Users wave a scanner over the device to obtain a reading.

Asked to comment, Nicholas Argento, MD, diabetes technology director at Maryland Endocrine and Diabetes, Columbia, told Medscape Medical News: “One of the biggest problems with access to continuous glucose monitoring is cost. Payers need to see that there’s some cost-saving to offset the cost of paying for these devices. I think both of these studies are important for that reason.”

However, Argento also said he recommends that people with type 1 diabetes use the Dexcom continuous glucose monitor (CGM) if possible rather than the Libre, despite the former’s higher cost, because it has an alarm feature that the Libre doesn’t and is more accurate in the hypoglycemic range.

Large French study: Libre cuts DKA hospitalizations by 50%

The FreeStyle Libre system has been reimbursed in France since June 1, 2017 for patients over 4 years of age with type 1 or type 2 diabetes who take at least 3 insulin injections per day or use an insulin pump.

Sara Freeman/MDedge News

The new results were presented by Ronan Roussel, MD, PhD, chief of the endocrinology, diabetes, and nutrition department at Hôpital Bichat, Fédération de Diabétologie, AP-HP, Paris, France.

The DKA hospitalization data Roussel reported were part of a larger longitudinal retrospective cohort study looking at overall prescribing and use of the Libre system, and its impact on healthcare outcomes and associated costs in standard practice in France. The data came from a large nationwide claims database containing all healthcare expenses for over 66 million people.

The current study participants were 74,076 individuals with at least a full year of follow-up beginning in 2017 with the date of first reimbursement for the FreeStyle Libre system. Of those, 44.8% (33,203) had type 1 diabetes and 55.2% (40,955) had type 2 diabetes.

Prior to initiation of Libre use, about a quarter of each group was using 0 fingerstick test strips per day, about 19% of the type 1 diabetes group and 28% of the type 2 diabetes group were using 1-3 strips per day, and about half of both groups were using 4 or more strips per day.

Compared with the year prior to the date of first reimbursement for the Libre, hospitalization rates for DKA during the first year of Libre use fell by 52% in the type 1 diabetes group, from 5.46 to 2.59 per 100 patient-years, and by 47% in the type 2 diabetes group, from 1.70 to 0.90 per 100 patient-years.

The impact of Libre on DKA hospitalizations was most dramatic among those not using any test strips prior to Libre use, with a 60% reduction for the type 1 diabetes group (8.31 to 3.31 per 100 patient-years) and a 51% reduction in the type 2 diabetes group (2.51 to 1.23 per 100 patient-years).

But interestingly, the next-biggest impact was among those who had been using more than 5 test strips per day, with drops of 59% among those with type 1 diabetes (5.55 to 2.26 per 100 patient-years) and 52% in the type 2 diabetes group (1.88 to 0.90 per 100 patient-years).

This finding is important for the United States, Argento said, because some insurers, including Medicare, require that the patient performs at least 4 fingerstick glucose measurements per day to qualify for reimbursement for the Libre or any CGM system.

“I think that speaks to the importance of not requiring that patients first show they’re frequently doing self-blood glucose monitoring before they can get these devices,” he observed.

The large benefit in the high strip use group is interesting too, Argento said. “It’s a different group of people. They’re more engaged in their care...This U-shaped curve they showed is fascinating.”

Reductions in DKA hospitalizations were also similar between patients using insulin pumps and those using multiple daily injections of insulin, Roussel reported.

“It is plausible that use of the FreeStyle Libre system allowed people to detect and limit persistent hyperglycemia, and subsequently ketoacidosis,” Roussel said.

“This analysis has significant implications for patient-centered clinical care in diabetes and also for long-term health economic outcomes in the treatment of diabetes at a national level.”

All-cause hospitalizations drop 30% with Libre in type 2 diabetes

Richard M. Bergenstal, MD, executive director of the International Diabetes Center at Park Nicollet, Minneapolis, Minnesota, presented the US results, obtained from the IBM Watson Health MarketScan, a database of commercial and Medicare supplemental insurance claims for over 30 million Americans.

The study population included 2463 patients with type 2 diabetes using basal-bolus daily insulin injections but who had not previously used Libre or any other CGM, and for whom data were available 6 months prior to and after Libre initiation.

Compared with 6 months prior to Libre use, the number of acute diabetes-related events — including hyperglycemia, hypoglycemia, DKA, hypoglycemic coma, and hyperosmolarity — in the subsequent 6 months dropped by 60%, from 0.180 to 0.072 events per patient-year (P < .001).

Similarly significant reductions were seen between males and females, and among those aged ≥ 50 years or < 50 years.

All-cause hospitalizations also significantly dropped by 33% (P < 0.001), from 0.420 to 0.283 events per patient-year. Among diagnostic codes for the hospitalizations, circulatory system causes remained number one during both time periods, with little change from pre-Libre to during Libre use.

However, “endocrine, nutritional, and metabolism system” codes dropped from the second position pre-Libre (6.4 events/100 patient-years) down to the fifth position (2.6 events/100 patient-years).

And, Bergenstal noted, other major diagnostic categories that also dropped included respiratory (3.5 to 2.1 events/100 patient-years), kidney and urinary tract (3.3 to 1.7 events/100 patient-years), and hepatobiliary system and pancreas (2.4 to 1.4 events/100 patient-years).

“We’re seeing a resurgence of certain types of complications, but all of these were reduced in the 6 months after Libre,” Bergenstal pointed out.

And, pertinent to the current COVID-19 situation, “infectious and parasitic disease and disorders” dropped as well, from 4.8 to 2.8 per 100 patient-years.

Argento commented: “The fact that infections went down speaks to something that is important right now. Hyperglycemia impairs immune function chronically, but also acutely...so patients who become ill and their blood glucose deteriorates rapidly are much more likely to have a poor outcome regardless of infection. There are data for COVID-19 now.”

“These findings provide compelling support for use of [Libre] to improve both clinical outcomes and potentially reduce costs in this patient population,” Bergenstal concluded.

Roussel has reported being on advisory panels for Abbott, AstraZeneca, Diabnext, Eli Lilly, Merck, Mundipharma International, Novo Nordisk, and Sanofi-Aventis. Bergenstal has reported being a consultant for Ascensia Diabetes Care, Johnson & Johnson, and has other relationships with Abbott, Dexcom, Hygieia, Lilly Diabetes, Medtronic, Novo Nordisk, Onduo, Roche Diabetes Care, Sanofi, and UnitedHealth Group. Argento has reported consulting and being on speaker bureaus for Omnipod, Eli Lilly, Novo Nordisk, Dexcom, and Boehringer Ingelheim.

This article first appeared on Medscape.com.
 

Drug adherence, healthcare use, medical costs, and heart failure rates were better among patients with type 2 diabetes who were newly prescribed a sodium-glucose cotransporter 2 (SGLT2) inhibitor than a glucagon-like peptide 1 (GLP-1) receptor agonist in a real-world, observational study.

Composite cardiovascular (CV) outcomes were similar between the two drug classes.

Insiya Poonawalla, PhD, a researcher at Humana Healthcare Research, Flower Mound, Texas, reported the study results in an oral presentation on June 12 at the virtual American Diabetes Association (ADA) 80th Scientific Sessions.

The investigators matched more than 10,000 patients with type 2 diabetes — half initiated on an SGLT2 inhibitor and half initiated on a GLP-1 agonist — from the Humana database of insurance claims data.

“These findings suggest potential benefits” of SGLT2 inhibitors, “particularly where risk related to heart failure is an important consideration,” Poonawalla said, but as always, any benefits need to be weighed against any risks.

And “while this study provides a pretty complete and current picture of claims until 2018,” it has limitations inherent to observational data (such as possible errors or omissions in the claims data), she conceded.

Mitchel L. Zoler/MDedge News

Mikhail Kosiborod, MD, invited to comment on the research, said this preliminary study was likely too short and small to definitively demonstrate differences in composite CV outcomes between the two drug classes, but he noted that the overall findings are not unexpected.

And often, the particular CV risk profile of an individual patient will point to one or the other of these drug classes as a best fit, he noted.

Too soon to alter clinical practice

Kosiborod, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said he nevertheless feels “it would be a bit premature to use these findings as a guide to change clinical practice.”

“The study is relatively small in scope and likely underpowered to examine CV outcomes,” he said in an email interview.

Larger population-based studies and ideally head-to-head randomized controlled trials of various type 2 diabetes agents could compare these two drug classes more definitively, he asserted.

In the meantime, safety profiles of both medication classes “have been well established — in tens of thousands of patients in clinical trials and millions of patients prescribed these therapies in clinical practice,” he noted.

In general, the drugs in both classes are well-tolerated and safe for most patients with type 2 diabetes when used appropriately.

“Certainly, patients with type 2 diabetes and established CV disease (or at high risk for CV complications) are ideal candidates for either an SGLT2 inhibitor or a GLP-1 receptor agonist,” Kosiborod said.

“Given the data we have from outcome trials, an SGLT2 inhibitor would be a better initial strategy in a patient with type 2 diabetes and heart failure (especially heart failure with reduced ejection fraction) and/or diabetic kidney disease,” he continued.

On the other hand, “a GLP-1 receptor agonist may be a better initial strategy in a type 2 diabetes patient with (or at very high risk for) atherosclerotic cardiovascular disease (ASCVD), especially if there is concomitant obesity contributing to the disease process.”

Limited comparisons of these two newer drug classes

“Real-world evidence comparing these two therapeutic classes based on CV outcomes is limited,” Poonawalla said at the start of her presentation, and relative treatment persistence, utilization, and cost data are even less well studied.

To investigate this, the researchers identified patients aged 19 to 89 years who were newly prescribed one of these two types of antidiabetic agents during January 1, 2015 through June 30, 2017.

Poonawalla and senior study author Phil Schwab, PhD, research lead, Humana Healthcare Research, Louisville, Kentucky, clarified the study design and findings in an email to this new organization.

The team matched 5507 patients initiated on a GLP-1 agonist with 5507 patients newly prescribed an SGLT2 inhibitor.

Patients were a mean age of 65 years and 53% were women.

More than a third (37%) had established ASCVD, including myocardial infarction (MI) (7.9%) and stroke (9.8%), and 11.5% had heart failure.

About two thirds were receiving metformin and about a third were receiving insulin.

In the GLP-1 agonist group, more than half of patients were prescribed liraglutide (57%), followed by dulaglutide (33%), exenatide, and lixisenatide (two patients).

In the SGLT2 inhibitor group, close to 70% received canagliflozin, about a quarter received empagliflozin, and the rest received dapagliflozin.

During up to 3.5 years of follow-up, a similar percentage of patients in each group had either an MI, stroke, or died (the primary composite CV outcome) (hazard ratio [HR], 0.98; 95% CI, 0.89 - 1.07).

However, more patients in the GLP-1 agonist group had heart failure or died (the secondary composite CV outcome), driven by a higher rate of heart failure in this group.

But after adjusting for time to events there was no significant between-group difference in the secondary composite CV outcome (HR, 1.09; 95% CI, 0.99 - 1.21).

During the 12-months after the initial prescription, patients who were started on a GLP-1 agonist versus an SGLT2 inhibitor had higher mean monthly medical costs, which included hospitalizations, emergency department (ED) visits, and outpatient visits ($904 vs $834; P < .001).

They also had higher pharmacy costs, which covered all drugs ($891 vs $783; P < .001).

And they were more likely to discontinue treatment (HR, 1.15; 95% CI, 1.10 - 1.21), be hospitalized (14.4% vs 11.9%; P < .001), or visit the ED (27.4% vs 23.5%; P < .001).

“Not too surprising” and “somewhat reassuring”

Overall, Kosiborod did not find the results surprising.

Given the sample size and follow-up time, event rates were probably quite low and insufficient to draw firm conclusions about the composite CV outcomes, he reiterated.

However, given the comparable effects of these two drug types on major adverse cardiac events (MACE) in similar patient populations with type 2 diabetes, it is not too surprising that there were no significant differences in these outcomes.

It was also “somewhat reassuring” to see that heart failure rates were lower with SGLT2 inhibitors, “as one would expect,” he said, because these agents “have been shown to significantly reduce the risk of hospitalization for heart failure in multiple outcome trials, whereas GLP-1 receptor agonists’ beneficial CV effects appear to be more limited to MACE reduction.”

The higher rates of discontinuation with GLP-1 receptor agonists “is also not a surprise, since patients experience more gastrointestinal tolerability issues with these agents (mainly nausea),” which can be mitigated in the majority of patients with appropriate education and close follow up — but is not done consistently.

Similarly, “the cost differences are also expected, since GLP-1 receptor agonists tend to be more expensive.”

On the other hand, the higher rates of hospitalizations with GLP-1 agonists compared to SGLT2 inhibitors “requires further exploration and confirmation,” Kosiborod said.

But he suspects this may be due to residual confounding, “since GLP-1 agonists are typically initiated later in the type 2 diabetes treatment algorithm,” so these patients could have lengthier, more difficult-to-manage type 2 diabetes with more comorbidities despite the propensity matching.

Poonawalla and Schwab are employed by Humana. Kosiborod has disclosed research support from AstraZeneca and Boehringer Ingelheim; honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and consulting fees from Amarin, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Glytec, Intarcia, Janssen, Merck, Novartis, Novo Nordisk, and Sanofi Aventis .



This article first appeared on Medscape.com

Drug adherence, healthcare use, medical costs, and heart failure rates were better among patients with type 2 diabetes who were newly prescribed a sodium-glucose cotransporter 2 (SGLT2) inhibitor than a glucagon-like peptide 1 (GLP-1) receptor agonist in a real-world, observational study.

Composite cardiovascular (CV) outcomes were similar between the two drug classes.

Insiya Poonawalla, PhD, a researcher at Humana Healthcare Research, Flower Mound, Texas, reported the study results in an oral presentation on June 12 at the virtual American Diabetes Association (ADA) 80th Scientific Sessions.

The investigators matched more than 10,000 patients with type 2 diabetes — half initiated on an SGLT2 inhibitor and half initiated on a GLP-1 agonist — from the Humana database of insurance claims data.

“These findings suggest potential benefits” of SGLT2 inhibitors, “particularly where risk related to heart failure is an important consideration,” Poonawalla said, but as always, any benefits need to be weighed against any risks.

And “while this study provides a pretty complete and current picture of claims until 2018,” it has limitations inherent to observational data (such as possible errors or omissions in the claims data), she conceded.

Mitchel L. Zoler/MDedge News

Mikhail Kosiborod, MD, invited to comment on the research, said this preliminary study was likely too short and small to definitively demonstrate differences in composite CV outcomes between the two drug classes, but he noted that the overall findings are not unexpected.

And often, the particular CV risk profile of an individual patient will point to one or the other of these drug classes as a best fit, he noted.

Too soon to alter clinical practice

Kosiborod, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said he nevertheless feels “it would be a bit premature to use these findings as a guide to change clinical practice.”

“The study is relatively small in scope and likely underpowered to examine CV outcomes,” he said in an email interview.

Larger population-based studies and ideally head-to-head randomized controlled trials of various type 2 diabetes agents could compare these two drug classes more definitively, he asserted.

In the meantime, safety profiles of both medication classes “have been well established — in tens of thousands of patients in clinical trials and millions of patients prescribed these therapies in clinical practice,” he noted.

In general, the drugs in both classes are well-tolerated and safe for most patients with type 2 diabetes when used appropriately.

“Certainly, patients with type 2 diabetes and established CV disease (or at high risk for CV complications) are ideal candidates for either an SGLT2 inhibitor or a GLP-1 receptor agonist,” Kosiborod said.

“Given the data we have from outcome trials, an SGLT2 inhibitor would be a better initial strategy in a patient with type 2 diabetes and heart failure (especially heart failure with reduced ejection fraction) and/or diabetic kidney disease,” he continued.

On the other hand, “a GLP-1 receptor agonist may be a better initial strategy in a type 2 diabetes patient with (or at very high risk for) atherosclerotic cardiovascular disease (ASCVD), especially if there is concomitant obesity contributing to the disease process.”

Limited comparisons of these two newer drug classes

“Real-world evidence comparing these two therapeutic classes based on CV outcomes is limited,” Poonawalla said at the start of her presentation, and relative treatment persistence, utilization, and cost data are even less well studied.

To investigate this, the researchers identified patients aged 19 to 89 years who were newly prescribed one of these two types of antidiabetic agents during January 1, 2015 through June 30, 2017.

Poonawalla and senior study author Phil Schwab, PhD, research lead, Humana Healthcare Research, Louisville, Kentucky, clarified the study design and findings in an email to this new organization.

The team matched 5507 patients initiated on a GLP-1 agonist with 5507 patients newly prescribed an SGLT2 inhibitor.

Patients were a mean age of 65 years and 53% were women.

More than a third (37%) had established ASCVD, including myocardial infarction (MI) (7.9%) and stroke (9.8%), and 11.5% had heart failure.

About two thirds were receiving metformin and about a third were receiving insulin.

In the GLP-1 agonist group, more than half of patients were prescribed liraglutide (57%), followed by dulaglutide (33%), exenatide, and lixisenatide (two patients).

In the SGLT2 inhibitor group, close to 70% received canagliflozin, about a quarter received empagliflozin, and the rest received dapagliflozin.

During up to 3.5 years of follow-up, a similar percentage of patients in each group had either an MI, stroke, or died (the primary composite CV outcome) (hazard ratio [HR], 0.98; 95% CI, 0.89 - 1.07).

However, more patients in the GLP-1 agonist group had heart failure or died (the secondary composite CV outcome), driven by a higher rate of heart failure in this group.

But after adjusting for time to events there was no significant between-group difference in the secondary composite CV outcome (HR, 1.09; 95% CI, 0.99 - 1.21).

During the 12-months after the initial prescription, patients who were started on a GLP-1 agonist versus an SGLT2 inhibitor had higher mean monthly medical costs, which included hospitalizations, emergency department (ED) visits, and outpatient visits ($904 vs $834; P < .001).

They also had higher pharmacy costs, which covered all drugs ($891 vs $783; P < .001).

And they were more likely to discontinue treatment (HR, 1.15; 95% CI, 1.10 - 1.21), be hospitalized (14.4% vs 11.9%; P < .001), or visit the ED (27.4% vs 23.5%; P < .001).

“Not too surprising” and “somewhat reassuring”

Overall, Kosiborod did not find the results surprising.

Given the sample size and follow-up time, event rates were probably quite low and insufficient to draw firm conclusions about the composite CV outcomes, he reiterated.

However, given the comparable effects of these two drug types on major adverse cardiac events (MACE) in similar patient populations with type 2 diabetes, it is not too surprising that there were no significant differences in these outcomes.

It was also “somewhat reassuring” to see that heart failure rates were lower with SGLT2 inhibitors, “as one would expect,” he said, because these agents “have been shown to significantly reduce the risk of hospitalization for heart failure in multiple outcome trials, whereas GLP-1 receptor agonists’ beneficial CV effects appear to be more limited to MACE reduction.”

The higher rates of discontinuation with GLP-1 receptor agonists “is also not a surprise, since patients experience more gastrointestinal tolerability issues with these agents (mainly nausea),” which can be mitigated in the majority of patients with appropriate education and close follow up — but is not done consistently.

Similarly, “the cost differences are also expected, since GLP-1 receptor agonists tend to be more expensive.”

On the other hand, the higher rates of hospitalizations with GLP-1 agonists compared to SGLT2 inhibitors “requires further exploration and confirmation,” Kosiborod said.

But he suspects this may be due to residual confounding, “since GLP-1 agonists are typically initiated later in the type 2 diabetes treatment algorithm,” so these patients could have lengthier, more difficult-to-manage type 2 diabetes with more comorbidities despite the propensity matching.

Poonawalla and Schwab are employed by Humana. Kosiborod has disclosed research support from AstraZeneca and Boehringer Ingelheim; honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and consulting fees from Amarin, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Glytec, Intarcia, Janssen, Merck, Novartis, Novo Nordisk, and Sanofi Aventis .



This article first appeared on Medscape.com

Drug adherence, healthcare use, medical costs, and heart failure rates were better among patients with type 2 diabetes who were newly prescribed a sodium-glucose cotransporter 2 (SGLT2) inhibitor than a glucagon-like peptide 1 (GLP-1) receptor agonist in a real-world, observational study.

Composite cardiovascular (CV) outcomes were similar between the two drug classes.

Insiya Poonawalla, PhD, a researcher at Humana Healthcare Research, Flower Mound, Texas, reported the study results in an oral presentation on June 12 at the virtual American Diabetes Association (ADA) 80th Scientific Sessions.

The investigators matched more than 10,000 patients with type 2 diabetes — half initiated on an SGLT2 inhibitor and half initiated on a GLP-1 agonist — from the Humana database of insurance claims data.

“These findings suggest potential benefits” of SGLT2 inhibitors, “particularly where risk related to heart failure is an important consideration,” Poonawalla said, but as always, any benefits need to be weighed against any risks.

And “while this study provides a pretty complete and current picture of claims until 2018,” it has limitations inherent to observational data (such as possible errors or omissions in the claims data), she conceded.

Mitchel L. Zoler/MDedge News

Mikhail Kosiborod, MD, invited to comment on the research, said this preliminary study was likely too short and small to definitively demonstrate differences in composite CV outcomes between the two drug classes, but he noted that the overall findings are not unexpected.

And often, the particular CV risk profile of an individual patient will point to one or the other of these drug classes as a best fit, he noted.

Too soon to alter clinical practice

Kosiborod, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said he nevertheless feels “it would be a bit premature to use these findings as a guide to change clinical practice.”

“The study is relatively small in scope and likely underpowered to examine CV outcomes,” he said in an email interview.

Larger population-based studies and ideally head-to-head randomized controlled trials of various type 2 diabetes agents could compare these two drug classes more definitively, he asserted.

In the meantime, safety profiles of both medication classes “have been well established — in tens of thousands of patients in clinical trials and millions of patients prescribed these therapies in clinical practice,” he noted.

In general, the drugs in both classes are well-tolerated and safe for most patients with type 2 diabetes when used appropriately.

“Certainly, patients with type 2 diabetes and established CV disease (or at high risk for CV complications) are ideal candidates for either an SGLT2 inhibitor or a GLP-1 receptor agonist,” Kosiborod said.

“Given the data we have from outcome trials, an SGLT2 inhibitor would be a better initial strategy in a patient with type 2 diabetes and heart failure (especially heart failure with reduced ejection fraction) and/or diabetic kidney disease,” he continued.

On the other hand, “a GLP-1 receptor agonist may be a better initial strategy in a type 2 diabetes patient with (or at very high risk for) atherosclerotic cardiovascular disease (ASCVD), especially if there is concomitant obesity contributing to the disease process.”

Limited comparisons of these two newer drug classes

“Real-world evidence comparing these two therapeutic classes based on CV outcomes is limited,” Poonawalla said at the start of her presentation, and relative treatment persistence, utilization, and cost data are even less well studied.

To investigate this, the researchers identified patients aged 19 to 89 years who were newly prescribed one of these two types of antidiabetic agents during January 1, 2015 through June 30, 2017.

Poonawalla and senior study author Phil Schwab, PhD, research lead, Humana Healthcare Research, Louisville, Kentucky, clarified the study design and findings in an email to this new organization.

The team matched 5507 patients initiated on a GLP-1 agonist with 5507 patients newly prescribed an SGLT2 inhibitor.

Patients were a mean age of 65 years and 53% were women.

More than a third (37%) had established ASCVD, including myocardial infarction (MI) (7.9%) and stroke (9.8%), and 11.5% had heart failure.

About two thirds were receiving metformin and about a third were receiving insulin.

In the GLP-1 agonist group, more than half of patients were prescribed liraglutide (57%), followed by dulaglutide (33%), exenatide, and lixisenatide (two patients).

In the SGLT2 inhibitor group, close to 70% received canagliflozin, about a quarter received empagliflozin, and the rest received dapagliflozin.

During up to 3.5 years of follow-up, a similar percentage of patients in each group had either an MI, stroke, or died (the primary composite CV outcome) (hazard ratio [HR], 0.98; 95% CI, 0.89 - 1.07).

However, more patients in the GLP-1 agonist group had heart failure or died (the secondary composite CV outcome), driven by a higher rate of heart failure in this group.

But after adjusting for time to events there was no significant between-group difference in the secondary composite CV outcome (HR, 1.09; 95% CI, 0.99 - 1.21).

During the 12-months after the initial prescription, patients who were started on a GLP-1 agonist versus an SGLT2 inhibitor had higher mean monthly medical costs, which included hospitalizations, emergency department (ED) visits, and outpatient visits ($904 vs $834; P < .001).

They also had higher pharmacy costs, which covered all drugs ($891 vs $783; P < .001).

And they were more likely to discontinue treatment (HR, 1.15; 95% CI, 1.10 - 1.21), be hospitalized (14.4% vs 11.9%; P < .001), or visit the ED (27.4% vs 23.5%; P < .001).

“Not too surprising” and “somewhat reassuring”

Overall, Kosiborod did not find the results surprising.

Given the sample size and follow-up time, event rates were probably quite low and insufficient to draw firm conclusions about the composite CV outcomes, he reiterated.

However, given the comparable effects of these two drug types on major adverse cardiac events (MACE) in similar patient populations with type 2 diabetes, it is not too surprising that there were no significant differences in these outcomes.

It was also “somewhat reassuring” to see that heart failure rates were lower with SGLT2 inhibitors, “as one would expect,” he said, because these agents “have been shown to significantly reduce the risk of hospitalization for heart failure in multiple outcome trials, whereas GLP-1 receptor agonists’ beneficial CV effects appear to be more limited to MACE reduction.”

The higher rates of discontinuation with GLP-1 receptor agonists “is also not a surprise, since patients experience more gastrointestinal tolerability issues with these agents (mainly nausea),” which can be mitigated in the majority of patients with appropriate education and close follow up — but is not done consistently.

Similarly, “the cost differences are also expected, since GLP-1 receptor agonists tend to be more expensive.”

On the other hand, the higher rates of hospitalizations with GLP-1 agonists compared to SGLT2 inhibitors “requires further exploration and confirmation,” Kosiborod said.

But he suspects this may be due to residual confounding, “since GLP-1 agonists are typically initiated later in the type 2 diabetes treatment algorithm,” so these patients could have lengthier, more difficult-to-manage type 2 diabetes with more comorbidities despite the propensity matching.

Poonawalla and Schwab are employed by Humana. Kosiborod has disclosed research support from AstraZeneca and Boehringer Ingelheim; honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and consulting fees from Amarin, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Glytec, Intarcia, Janssen, Merck, Novartis, Novo Nordisk, and Sanofi Aventis .



This article first appeared on Medscape.com

For patients with painful diabetic neuropathy that doesn’t resolve with standard treatment, use of a 10-kHz spinal cord stimulation device may relieve pain and improve sensation, initial results of a large randomized controlled trial suggest.

Some 79% of patients had substantial pain relief 3 months after starting treatment, compared with 5% of patients managed with conventional medical treatment, according to results of SENZA-PDN, which investigators say is the largest-ever randomized, controlled trial of spinal cord stimulation for managing painful diabetic neuropathy.

Although this was not a comparative trial, investigator Erika Petersen, MD, said in an interview that results seen with the 10-kHz spinal cord stimulator (Nevro Corp.) exceed what has been seen in previous studies of spinal cord stimulation devices operating at lower frequencies, where response rates have been in the 40%-55% range.

New option for front line providers?

“My overall takeaway here is that these initial 3-month results are very promising,” said Dr. Petersen, who is Director of Functional & Restorative Neurosurgery and Neuromodulation at the University of Arkansas for Medical Sciences in Little Rock.

Patient-perceived numbness and sensory assessments by investigators also improved following implantation of the spinal cord stimulator, according to Dr. Peterson, who added that measurements of sleep and activity also seemed to improve in these patients with painful diabetic neuropathy.

“Spinal cord stimulation has been established for chronic back and leg pain, but being able to innovate in this population with diabetic neuropathy is really something that we anticipate will improve quality of life and functional benefit for a large number of patients who currently have been stuck with the options that are currently available,” Dr. Petersen said in an interview.

Courtesy Mayo Clinic

Natalie H. Strand, MD, assistant professor of pain medicine at Mayo Clinic, Scottsdale, Ariz., said that while the findings of this randomized study may require corroboration, they do suggest that this neuromodulation device may provide another option for front line diabetes providers when patients have persistent pain despite appropriately medication management.

“These patients are probably under-referred to interventional pain specialists,” said Dr. Strand in an interview. “The primary care physicians and endocrinologists may not think of neuromodulation as an appropriate treatment, and they may not know that it can be so effective.”

“Anything that we can add as physicians to help decrease the burden of diabetes is going to be very impactful,” Dr. Strand added. “While this is focused on pain, what we’re really trying to treat is the entire patient – improve their quality of life and make diabetes more manageable.”

Nearly 80% of treated patients responded at 3 months

The SENZA-PDN study results were presented as a late-breaking poster presentation at the virtual annual scientific sessions of the American Diabetes Association. Those results included 103 patients randomized to conventional medical management alone, and 113 who received medical management plus the spinal cord stimulator, which Dr. Strand described as a minimally invasive, reversibly implanted epidural device designed to stimulate the spinal cord and reverse pain sensations.

The median age was about 61 years and roughly two-thirds were male. All patients had to have lower extremity pain with an average intensity of at least 5 out of 10 cm on the visual analog scale (VAS) at enrollment, according to published inclusion criteria for the study (NCT03228420).

Three months after device implantation, 75 out of 95 evaluable patients (79%) had a response, defined as 50% or greater pain relief plus no worsening of neurological deficit related to painful diabetic neuropathy. By contrast, only 5 of 94 medically managed patients (5%) met those response criteria (P < 0.001), according to reported data.

The mean VAS score in the device group dropped from 7.6 at baseline to 2.4 at 1 month and 1.7 at 3 months, data show. In the medical management group, mean VAS scores were 7.0 at baseline, 6.7 at 1 month, and 6.5 at 3 months.

Sensory assessment of monofilament and pinprick perception, performed by investigators at 3 months, indicated a 72% improvement in the device arm versus 7% improvement in the medical management arm, while analysis of patient-drawn diagrams additionally suggested improvement in perceived numbness, according to investigators.

Quality-of-life improvements related to sleep and activity were also apparent at 3 months in the device group, Dr. Petersen said, with investigators noting substantial reductions in trouble falling asleep because of pain and awakening due to pain. Likewise, data at this initial report suggested improvements in 6-minute walk test that were apparent in the device group but not the medical management group.


While the spinal cord stimulator under investigation is already approved by the U.S. Food and Drug Administration, Dr. Petersen said a lack of data specific to painful diabetic neuropathy has been a hurdle to insurance coverage for some patients.

“I’ve had patients who clearly have every suggestion that they match the characteristics of our research population here, but the insurance will decline the procedure as being experimental,” she said. “My hope is that randomized, controlled trial results in a research study such as this is something that will improve the access of the therapy to patients who would not be able to afford it without having insurance cover the procedure.”

Follow-up of the study will continue for 24 months and will include assessment of health economics and use of pain medication, Dr. Petersen said.

The SENZA-PDN study is funded by Nevro Corp. Dr. Petersen said that she receives research funding and consulting fees from Nevro Corp. and other device manufacturers. Dr. Strand said she had no disclosures related to the research.

cardnews@mdedge.com

SOURCE: Petersen E. ADA 2020, Late-breaking poster 31-LB.

For patients with painful diabetic neuropathy that doesn’t resolve with standard treatment, use of a 10-kHz spinal cord stimulation device may relieve pain and improve sensation, initial results of a large randomized controlled trial suggest.

Some 79% of patients had substantial pain relief 3 months after starting treatment, compared with 5% of patients managed with conventional medical treatment, according to results of SENZA-PDN, which investigators say is the largest-ever randomized, controlled trial of spinal cord stimulation for managing painful diabetic neuropathy.

Although this was not a comparative trial, investigator Erika Petersen, MD, said in an interview that results seen with the 10-kHz spinal cord stimulator (Nevro Corp.) exceed what has been seen in previous studies of spinal cord stimulation devices operating at lower frequencies, where response rates have been in the 40%-55% range.

New option for front line providers?

“My overall takeaway here is that these initial 3-month results are very promising,” said Dr. Petersen, who is Director of Functional & Restorative Neurosurgery and Neuromodulation at the University of Arkansas for Medical Sciences in Little Rock.

Patient-perceived numbness and sensory assessments by investigators also improved following implantation of the spinal cord stimulator, according to Dr. Peterson, who added that measurements of sleep and activity also seemed to improve in these patients with painful diabetic neuropathy.

“Spinal cord stimulation has been established for chronic back and leg pain, but being able to innovate in this population with diabetic neuropathy is really something that we anticipate will improve quality of life and functional benefit for a large number of patients who currently have been stuck with the options that are currently available,” Dr. Petersen said in an interview.

Courtesy Mayo Clinic

Natalie H. Strand, MD, assistant professor of pain medicine at Mayo Clinic, Scottsdale, Ariz., said that while the findings of this randomized study may require corroboration, they do suggest that this neuromodulation device may provide another option for front line diabetes providers when patients have persistent pain despite appropriately medication management.

“These patients are probably under-referred to interventional pain specialists,” said Dr. Strand in an interview. “The primary care physicians and endocrinologists may not think of neuromodulation as an appropriate treatment, and they may not know that it can be so effective.”

“Anything that we can add as physicians to help decrease the burden of diabetes is going to be very impactful,” Dr. Strand added. “While this is focused on pain, what we’re really trying to treat is the entire patient – improve their quality of life and make diabetes more manageable.”

Nearly 80% of treated patients responded at 3 months

The SENZA-PDN study results were presented as a late-breaking poster presentation at the virtual annual scientific sessions of the American Diabetes Association. Those results included 103 patients randomized to conventional medical management alone, and 113 who received medical management plus the spinal cord stimulator, which Dr. Strand described as a minimally invasive, reversibly implanted epidural device designed to stimulate the spinal cord and reverse pain sensations.

The median age was about 61 years and roughly two-thirds were male. All patients had to have lower extremity pain with an average intensity of at least 5 out of 10 cm on the visual analog scale (VAS) at enrollment, according to published inclusion criteria for the study (NCT03228420).

Three months after device implantation, 75 out of 95 evaluable patients (79%) had a response, defined as 50% or greater pain relief plus no worsening of neurological deficit related to painful diabetic neuropathy. By contrast, only 5 of 94 medically managed patients (5%) met those response criteria (P < 0.001), according to reported data.

The mean VAS score in the device group dropped from 7.6 at baseline to 2.4 at 1 month and 1.7 at 3 months, data show. In the medical management group, mean VAS scores were 7.0 at baseline, 6.7 at 1 month, and 6.5 at 3 months.

Sensory assessment of monofilament and pinprick perception, performed by investigators at 3 months, indicated a 72% improvement in the device arm versus 7% improvement in the medical management arm, while analysis of patient-drawn diagrams additionally suggested improvement in perceived numbness, according to investigators.

Quality-of-life improvements related to sleep and activity were also apparent at 3 months in the device group, Dr. Petersen said, with investigators noting substantial reductions in trouble falling asleep because of pain and awakening due to pain. Likewise, data at this initial report suggested improvements in 6-minute walk test that were apparent in the device group but not the medical management group.


While the spinal cord stimulator under investigation is already approved by the U.S. Food and Drug Administration, Dr. Petersen said a lack of data specific to painful diabetic neuropathy has been a hurdle to insurance coverage for some patients.

“I’ve had patients who clearly have every suggestion that they match the characteristics of our research population here, but the insurance will decline the procedure as being experimental,” she said. “My hope is that randomized, controlled trial results in a research study such as this is something that will improve the access of the therapy to patients who would not be able to afford it without having insurance cover the procedure.”

Follow-up of the study will continue for 24 months and will include assessment of health economics and use of pain medication, Dr. Petersen said.

The SENZA-PDN study is funded by Nevro Corp. Dr. Petersen said that she receives research funding and consulting fees from Nevro Corp. and other device manufacturers. Dr. Strand said she had no disclosures related to the research.

cardnews@mdedge.com

SOURCE: Petersen E. ADA 2020, Late-breaking poster 31-LB.

For patients with painful diabetic neuropathy that doesn’t resolve with standard treatment, use of a 10-kHz spinal cord stimulation device may relieve pain and improve sensation, initial results of a large randomized controlled trial suggest.

Some 79% of patients had substantial pain relief 3 months after starting treatment, compared with 5% of patients managed with conventional medical treatment, according to results of SENZA-PDN, which investigators say is the largest-ever randomized, controlled trial of spinal cord stimulation for managing painful diabetic neuropathy.

Although this was not a comparative trial, investigator Erika Petersen, MD, said in an interview that results seen with the 10-kHz spinal cord stimulator (Nevro Corp.) exceed what has been seen in previous studies of spinal cord stimulation devices operating at lower frequencies, where response rates have been in the 40%-55% range.

New option for front line providers?

“My overall takeaway here is that these initial 3-month results are very promising,” said Dr. Petersen, who is Director of Functional & Restorative Neurosurgery and Neuromodulation at the University of Arkansas for Medical Sciences in Little Rock.

Patient-perceived numbness and sensory assessments by investigators also improved following implantation of the spinal cord stimulator, according to Dr. Peterson, who added that measurements of sleep and activity also seemed to improve in these patients with painful diabetic neuropathy.

“Spinal cord stimulation has been established for chronic back and leg pain, but being able to innovate in this population with diabetic neuropathy is really something that we anticipate will improve quality of life and functional benefit for a large number of patients who currently have been stuck with the options that are currently available,” Dr. Petersen said in an interview.

Courtesy Mayo Clinic

Natalie H. Strand, MD, assistant professor of pain medicine at Mayo Clinic, Scottsdale, Ariz., said that while the findings of this randomized study may require corroboration, they do suggest that this neuromodulation device may provide another option for front line diabetes providers when patients have persistent pain despite appropriately medication management.

“These patients are probably under-referred to interventional pain specialists,” said Dr. Strand in an interview. “The primary care physicians and endocrinologists may not think of neuromodulation as an appropriate treatment, and they may not know that it can be so effective.”

“Anything that we can add as physicians to help decrease the burden of diabetes is going to be very impactful,” Dr. Strand added. “While this is focused on pain, what we’re really trying to treat is the entire patient – improve their quality of life and make diabetes more manageable.”

Nearly 80% of treated patients responded at 3 months

The SENZA-PDN study results were presented as a late-breaking poster presentation at the virtual annual scientific sessions of the American Diabetes Association. Those results included 103 patients randomized to conventional medical management alone, and 113 who received medical management plus the spinal cord stimulator, which Dr. Strand described as a minimally invasive, reversibly implanted epidural device designed to stimulate the spinal cord and reverse pain sensations.

The median age was about 61 years and roughly two-thirds were male. All patients had to have lower extremity pain with an average intensity of at least 5 out of 10 cm on the visual analog scale (VAS) at enrollment, according to published inclusion criteria for the study (NCT03228420).

Three months after device implantation, 75 out of 95 evaluable patients (79%) had a response, defined as 50% or greater pain relief plus no worsening of neurological deficit related to painful diabetic neuropathy. By contrast, only 5 of 94 medically managed patients (5%) met those response criteria (P < 0.001), according to reported data.

The mean VAS score in the device group dropped from 7.6 at baseline to 2.4 at 1 month and 1.7 at 3 months, data show. In the medical management group, mean VAS scores were 7.0 at baseline, 6.7 at 1 month, and 6.5 at 3 months.

Sensory assessment of monofilament and pinprick perception, performed by investigators at 3 months, indicated a 72% improvement in the device arm versus 7% improvement in the medical management arm, while analysis of patient-drawn diagrams additionally suggested improvement in perceived numbness, according to investigators.

Quality-of-life improvements related to sleep and activity were also apparent at 3 months in the device group, Dr. Petersen said, with investigators noting substantial reductions in trouble falling asleep because of pain and awakening due to pain. Likewise, data at this initial report suggested improvements in 6-minute walk test that were apparent in the device group but not the medical management group.


While the spinal cord stimulator under investigation is already approved by the U.S. Food and Drug Administration, Dr. Petersen said a lack of data specific to painful diabetic neuropathy has been a hurdle to insurance coverage for some patients.

“I’ve had patients who clearly have every suggestion that they match the characteristics of our research population here, but the insurance will decline the procedure as being experimental,” she said. “My hope is that randomized, controlled trial results in a research study such as this is something that will improve the access of the therapy to patients who would not be able to afford it without having insurance cover the procedure.”

Follow-up of the study will continue for 24 months and will include assessment of health economics and use of pain medication, Dr. Petersen said.

The SENZA-PDN study is funded by Nevro Corp. Dr. Petersen said that she receives research funding and consulting fees from Nevro Corp. and other device manufacturers. Dr. Strand said she had no disclosures related to the research.

cardnews@mdedge.com

SOURCE: Petersen E. ADA 2020, Late-breaking poster 31-LB.

Roughly half of adolescents and young adults with either type 1 or type 2 diabetes for about a decade had diastolic dysfunction, a direct precursor to heart failure, in a multicenter echocardiography survey of 479 American patients.

Courtesy Cincinnati Children&#039;s Hospital Medical Center

Using tissue Doppler echocardiography findings from 258 adolescents and young adults with type 1 diabetes, and 221 with type 2 diabetes, the study found at least one imaging marker of ventricular stiffness – diastolic dysfunction – in 58% of the patients with type 2 diabetes and in 47% of those with type 1 diabetes. The type 1 patients averaged 21 years of age with a median 12 years of diagnosed disease, while the type 2 patients had an average age of 25 years and a median 11 years disease duration.

The analysis also identified several measures that significantly linked with the presence of diastolic dysfunction: older age, female sex, nonwhite race, type 2 diabetes, higher heart rate, higher body mass index, higher systolic blood pressure, and higher hemoglobin A_1c.

“Our data suggest targeting modifiable risk factors” in these patients in an effort to slow the process causing the diastolic dysfunction, Amy S. Shah, MD, said at the virtual annual scientific sessions of the American Diabetes Association. She particularly cited interventions aimed at reducing body mass index, lowering blood pressure, and improving glycemic control, as well as preventing type 2 diabetes in the first place.

Prevention of type 2 diabetes, as well as prevention of diastolic dysfunction development and progression, are key steps because of the substantial clinical consequences of diastolic dysfunction, triggered by stiffening of the left ventricle. Diastolic dysfunction leads to increased left ventricular diastolic pressure, left atrial dysfunction, and ultimately heart failure with preserved ejection fraction, a common diabetes complication that currently has no treatment with proven efficacy, said Dr. Shah, a pediatric endocrinologist and director of the Adolescent Type 2 Diabetes Program at Cincinnati Children’s Hospital Medical Center.

“It’s very concerning that diastolic dysfunction is so prevalent in this age group,” commented Robert A. Gabbay, MD, Chief Science & Medical Officer of the American Diabetes Association. “An important question is whether you can see an improvement by reversing risk factors.” He noted the importance of confirming the finding in additional cohorts as well as running prospective studies looking at the impact of risk factor modification.

Dr. Shah and her associates used data collected at four U.S. centers from patients enrolled in the SEARCH for Diabetes in Youth study who underwent a tissue Doppler examination during 2016-2019, and used three measures derived from the scans to identify diastolic dysfunction:

• The E/A ratio, which compares the early flow wave across the mitral valve (E) with the atrial flow wave (A) that occurs after atrial contraction. Lower values reflect worse pathology.
• The E/e’ ratio, which compares the early flow wave across the mitral valve (E) with the rate of cardiac wall relaxation in early diastole (e’). Higher values reflect worse pathology.
• The e’/a’ ratio, which compares the rate of cardiac wall relaxation in early diastole (e’) with the rate of cardiac wall relaxation in late diastole (a’). Lower values reflect worse pathology.

The most common abnormality involved the e’/a’ measure, which occurred in roughly 38% of the patients with type 2 diabetes and in about 23% of those with type 1 diabetes. Next most common was an abnormally high E/e’ ratio, and fewer than 10% of patients had an abnormally low E/A ratio. Both the E/A and E/e’ values were significantly worse among patients with type 2 diabetes compared with type 1 patients, while no statistically significant difference separated the two subgroups for prevalence of an e’/a’ abnormality after adjustment for body mass index, blood pressure, and HbA_1c values.

Average body mass index among the 221 studied patients with type 2 diabetes was 38 kg/m², 74% were girls or women, and 57% were non-Hispanic black and 24% non-Hispanic white. Mean blood pressure among the patients with type 2 diabetes was 123/80 mm Hg, while it was 110/72 mm Hg among the 258 patients with type 1 diabetes.

SEARCH for Diabetes in Youth receives no commercial funding. Dr. Shah had no disclosures.

mzoler@mdedge.com

SOURCE: Shah AS et al. ADA 2020 abstract 58-OR.

Roughly half of adolescents and young adults with either type 1 or type 2 diabetes for about a decade had diastolic dysfunction, a direct precursor to heart failure, in a multicenter echocardiography survey of 479 American patients.

Courtesy Cincinnati Children&#039;s Hospital Medical Center

Using tissue Doppler echocardiography findings from 258 adolescents and young adults with type 1 diabetes, and 221 with type 2 diabetes, the study found at least one imaging marker of ventricular stiffness – diastolic dysfunction – in 58% of the patients with type 2 diabetes and in 47% of those with type 1 diabetes. The type 1 patients averaged 21 years of age with a median 12 years of diagnosed disease, while the type 2 patients had an average age of 25 years and a median 11 years disease duration.

The analysis also identified several measures that significantly linked with the presence of diastolic dysfunction: older age, female sex, nonwhite race, type 2 diabetes, higher heart rate, higher body mass index, higher systolic blood pressure, and higher hemoglobin A_1c.

“Our data suggest targeting modifiable risk factors” in these patients in an effort to slow the process causing the diastolic dysfunction, Amy S. Shah, MD, said at the virtual annual scientific sessions of the American Diabetes Association. She particularly cited interventions aimed at reducing body mass index, lowering blood pressure, and improving glycemic control, as well as preventing type 2 diabetes in the first place.

Prevention of type 2 diabetes, as well as prevention of diastolic dysfunction development and progression, are key steps because of the substantial clinical consequences of diastolic dysfunction, triggered by stiffening of the left ventricle. Diastolic dysfunction leads to increased left ventricular diastolic pressure, left atrial dysfunction, and ultimately heart failure with preserved ejection fraction, a common diabetes complication that currently has no treatment with proven efficacy, said Dr. Shah, a pediatric endocrinologist and director of the Adolescent Type 2 Diabetes Program at Cincinnati Children’s Hospital Medical Center.

“It’s very concerning that diastolic dysfunction is so prevalent in this age group,” commented Robert A. Gabbay, MD, Chief Science & Medical Officer of the American Diabetes Association. “An important question is whether you can see an improvement by reversing risk factors.” He noted the importance of confirming the finding in additional cohorts as well as running prospective studies looking at the impact of risk factor modification.

Dr. Shah and her associates used data collected at four U.S. centers from patients enrolled in the SEARCH for Diabetes in Youth study who underwent a tissue Doppler examination during 2016-2019, and used three measures derived from the scans to identify diastolic dysfunction:

• The E/A ratio, which compares the early flow wave across the mitral valve (E) with the atrial flow wave (A) that occurs after atrial contraction. Lower values reflect worse pathology.
• The E/e’ ratio, which compares the early flow wave across the mitral valve (E) with the rate of cardiac wall relaxation in early diastole (e’). Higher values reflect worse pathology.
• The e’/a’ ratio, which compares the rate of cardiac wall relaxation in early diastole (e’) with the rate of cardiac wall relaxation in late diastole (a’). Lower values reflect worse pathology.

The most common abnormality involved the e’/a’ measure, which occurred in roughly 38% of the patients with type 2 diabetes and in about 23% of those with type 1 diabetes. Next most common was an abnormally high E/e’ ratio, and fewer than 10% of patients had an abnormally low E/A ratio. Both the E/A and E/e’ values were significantly worse among patients with type 2 diabetes compared with type 1 patients, while no statistically significant difference separated the two subgroups for prevalence of an e’/a’ abnormality after adjustment for body mass index, blood pressure, and HbA_1c values.

Average body mass index among the 221 studied patients with type 2 diabetes was 38 kg/m², 74% were girls or women, and 57% were non-Hispanic black and 24% non-Hispanic white. Mean blood pressure among the patients with type 2 diabetes was 123/80 mm Hg, while it was 110/72 mm Hg among the 258 patients with type 1 diabetes.

SEARCH for Diabetes in Youth receives no commercial funding. Dr. Shah had no disclosures.

mzoler@mdedge.com

SOURCE: Shah AS et al. ADA 2020 abstract 58-OR.

Roughly half of adolescents and young adults with either type 1 or type 2 diabetes for about a decade had diastolic dysfunction, a direct precursor to heart failure, in a multicenter echocardiography survey of 479 American patients.

Courtesy Cincinnati Children&#039;s Hospital Medical Center

Using tissue Doppler echocardiography findings from 258 adolescents and young adults with type 1 diabetes, and 221 with type 2 diabetes, the study found at least one imaging marker of ventricular stiffness – diastolic dysfunction – in 58% of the patients with type 2 diabetes and in 47% of those with type 1 diabetes. The type 1 patients averaged 21 years of age with a median 12 years of diagnosed disease, while the type 2 patients had an average age of 25 years and a median 11 years disease duration.

The analysis also identified several measures that significantly linked with the presence of diastolic dysfunction: older age, female sex, nonwhite race, type 2 diabetes, higher heart rate, higher body mass index, higher systolic blood pressure, and higher hemoglobin A_1c.

“Our data suggest targeting modifiable risk factors” in these patients in an effort to slow the process causing the diastolic dysfunction, Amy S. Shah, MD, said at the virtual annual scientific sessions of the American Diabetes Association. She particularly cited interventions aimed at reducing body mass index, lowering blood pressure, and improving glycemic control, as well as preventing type 2 diabetes in the first place.

Prevention of type 2 diabetes, as well as prevention of diastolic dysfunction development and progression, are key steps because of the substantial clinical consequences of diastolic dysfunction, triggered by stiffening of the left ventricle. Diastolic dysfunction leads to increased left ventricular diastolic pressure, left atrial dysfunction, and ultimately heart failure with preserved ejection fraction, a common diabetes complication that currently has no treatment with proven efficacy, said Dr. Shah, a pediatric endocrinologist and director of the Adolescent Type 2 Diabetes Program at Cincinnati Children’s Hospital Medical Center.

“It’s very concerning that diastolic dysfunction is so prevalent in this age group,” commented Robert A. Gabbay, MD, Chief Science & Medical Officer of the American Diabetes Association. “An important question is whether you can see an improvement by reversing risk factors.” He noted the importance of confirming the finding in additional cohorts as well as running prospective studies looking at the impact of risk factor modification.

Dr. Shah and her associates used data collected at four U.S. centers from patients enrolled in the SEARCH for Diabetes in Youth study who underwent a tissue Doppler examination during 2016-2019, and used three measures derived from the scans to identify diastolic dysfunction:

• The E/A ratio, which compares the early flow wave across the mitral valve (E) with the atrial flow wave (A) that occurs after atrial contraction. Lower values reflect worse pathology.
• The E/e’ ratio, which compares the early flow wave across the mitral valve (E) with the rate of cardiac wall relaxation in early diastole (e’). Higher values reflect worse pathology.
• The e’/a’ ratio, which compares the rate of cardiac wall relaxation in early diastole (e’) with the rate of cardiac wall relaxation in late diastole (a’). Lower values reflect worse pathology.

The most common abnormality involved the e’/a’ measure, which occurred in roughly 38% of the patients with type 2 diabetes and in about 23% of those with type 1 diabetes. Next most common was an abnormally high E/e’ ratio, and fewer than 10% of patients had an abnormally low E/A ratio. Both the E/A and E/e’ values were significantly worse among patients with type 2 diabetes compared with type 1 patients, while no statistically significant difference separated the two subgroups for prevalence of an e’/a’ abnormality after adjustment for body mass index, blood pressure, and HbA_1c values.

Average body mass index among the 221 studied patients with type 2 diabetes was 38 kg/m², 74% were girls or women, and 57% were non-Hispanic black and 24% non-Hispanic white. Mean blood pressure among the patients with type 2 diabetes was 123/80 mm Hg, while it was 110/72 mm Hg among the 258 patients with type 1 diabetes.

SEARCH for Diabetes in Youth receives no commercial funding. Dr. Shah had no disclosures.

mzoler@mdedge.com

SOURCE: Shah AS et al. ADA 2020 abstract 58-OR.

Racial and socioeconomic disparities may be impeding access to newer diabetes medications among U.S. patients who may need them the most, according to researchers at the virtual annual scientific sessions of the American Diabetes Association.

Initiation of DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors was less likely among racial/ethnic minorities and Medicare Advantage beneficiaries in the retrospective analyses, leading the investigators to call for a better understanding of nonclinical factors that may be influencing treatment decisions.

Odds of new diabetes medication use were 55%-69% lower in patients in Medicare Advantage (MA) as compared to patients in commercial health plans, according to results of a separate study presented by Rozalina McCoy, MD, endocrinologist and researcher with Mayo Clinic, Rochester, Minn.

“The rates of use are increasing over time, but not enough in MA beneficiaries,” she said in her virtual presentation. “I think it really calls for more to be done to ensure access to and use of evidence based medications, by all people with type 2 diabetes.”

The likelihood of initiating a new diabetes drug was 29% lower among African Americans and 49% lower among Native Americans in a study of enrollees in the Look AHEAD (Action for Health in Diabetes) randomized trial, according to researcher Ahmed Elhussein, BMBCh, MPH, of the Johns Hopkins Bloomberg School of Public Health.

“This is particularly concerning, because they might have a greater need for these new diabetes medications, but reduced access,” Dr. Elhussein said in his presentation.

Disparities by race in diabetes drug use

The prevalence of type 2 diabetes in the United States is higher among racial and ethnic minorities, at about 12%-15%, versus about 7% in whites, according to Dr. Elhussein,

While the newer classes of diabetes medications have a lower risk of hyperglycemia and have cardiovascular and renal benefits, they also come at a higher cost, he added.

“This has created some concerns about access in particular for underserved groups,” he said in his presentation.

In their retrospective analysis, based on 4,892 patients enrolled in the Look AHEAD (Action for Health in Diabetes) randomized trial, Dr. Elhussein and coinvestigators identified 44% who had initiated a newer diabetes medication over a median follow-up of about 8 years.

They found black race was associated with significantly lower initiation of newer medications compared to whites, with a hazard ratio of 0.81 (95% confidence interval 0.80-0.94; P = 0.019), after adjustment for socioeconomic status.

New diabetes medication use was also significantly lower among American Indian/Alaskan Natives, with an HR of 0.51 and a confidence interval that did not include the null value of 1, according to the investigator.

No significant differences in new diabetes drug use were seen in Hispanics or those classified as other race/ethnicity, he added.

“We’d advocate for more study to try to understand what are the drivers of this disparity,” he said. “This would let us develop interventions that might help to increase access in these patient groups that might need them the most.”

Insurance type and diabetes drugs

Second-line medications, including GLP-1 receptor agonists and SGLT2 inhibitors, have “preferred” efficacy and side effect profiles, but are more costly than older, generic options such as sulfonylureas, which may affect the likelihood of their use, said Dr. McCoy, the Mayo Clinic researcher and lead author of the study on diabetes medication use by insurance type.

They analyzed 1.7 million individuals in a de-identified dataset (OptumLabs Data Warehouse) who were either privately insured or beneficiaries of Medicare Advantage, the private health plan alternative to fee-for-service Medicare.

After adjusting for race/ethnicity, baseline medications, age, gender, and other factors, odds of new medication use were significantly lower in the Medicare Advantage group, according to Dr. McCoy.

Odds ratios ranged from 0.61 (95% CI, 0.60-0.63) for DPP-4 inhibitors, to 0.45 (95% CI, 0.44-0.46) for GLP-1 receptor agonists, and to 0.31 (95% CI, 0.30-0.31) for SGLT2 inhibitors, she reported.

“This may be driven by affordability, because patients with Medicare Advantage plans are not able to access prescription savings cards (as compared to Medicare beneficiaries) and they also are more likely to have fixed incomes and not be able to afford the high costs of these drugs,” she said.

Dr. Elhussein reported no disclosures related to the research, while co-authors provided disclosures related to Abbott, Bigfoot Biomedical, Boehringer Ingelheim, Eli Lilly, MannKind, Medscape, Novo Nordisk, Sanofi US, and others. Dr McCoy likewise had no disclosures, while co-authors indicated disclosures related to Janssen Pharmaceuticals, the Centers for Medicare and Medicaid Services, and the U.S. Food and Drug Administration.

SOURCES: ADA 2020. Authors: McCoy R et al (38-OR), and Elhussein A, et al (37-OR).
 

Racial and socioeconomic disparities may be impeding access to newer diabetes medications among U.S. patients who may need them the most, according to researchers at the virtual annual scientific sessions of the American Diabetes Association.

Initiation of DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors was less likely among racial/ethnic minorities and Medicare Advantage beneficiaries in the retrospective analyses, leading the investigators to call for a better understanding of nonclinical factors that may be influencing treatment decisions.

Odds of new diabetes medication use were 55%-69% lower in patients in Medicare Advantage (MA) as compared to patients in commercial health plans, according to results of a separate study presented by Rozalina McCoy, MD, endocrinologist and researcher with Mayo Clinic, Rochester, Minn.

“The rates of use are increasing over time, but not enough in MA beneficiaries,” she said in her virtual presentation. “I think it really calls for more to be done to ensure access to and use of evidence based medications, by all people with type 2 diabetes.”

The likelihood of initiating a new diabetes drug was 29% lower among African Americans and 49% lower among Native Americans in a study of enrollees in the Look AHEAD (Action for Health in Diabetes) randomized trial, according to researcher Ahmed Elhussein, BMBCh, MPH, of the Johns Hopkins Bloomberg School of Public Health.

“This is particularly concerning, because they might have a greater need for these new diabetes medications, but reduced access,” Dr. Elhussein said in his presentation.

Disparities by race in diabetes drug use

The prevalence of type 2 diabetes in the United States is higher among racial and ethnic minorities, at about 12%-15%, versus about 7% in whites, according to Dr. Elhussein,

While the newer classes of diabetes medications have a lower risk of hyperglycemia and have cardiovascular and renal benefits, they also come at a higher cost, he added.

“This has created some concerns about access in particular for underserved groups,” he said in his presentation.

In their retrospective analysis, based on 4,892 patients enrolled in the Look AHEAD (Action for Health in Diabetes) randomized trial, Dr. Elhussein and coinvestigators identified 44% who had initiated a newer diabetes medication over a median follow-up of about 8 years.

They found black race was associated with significantly lower initiation of newer medications compared to whites, with a hazard ratio of 0.81 (95% confidence interval 0.80-0.94; P = 0.019), after adjustment for socioeconomic status.

New diabetes medication use was also significantly lower among American Indian/Alaskan Natives, with an HR of 0.51 and a confidence interval that did not include the null value of 1, according to the investigator.

No significant differences in new diabetes drug use were seen in Hispanics or those classified as other race/ethnicity, he added.

“We’d advocate for more study to try to understand what are the drivers of this disparity,” he said. “This would let us develop interventions that might help to increase access in these patient groups that might need them the most.”

Insurance type and diabetes drugs

Second-line medications, including GLP-1 receptor agonists and SGLT2 inhibitors, have “preferred” efficacy and side effect profiles, but are more costly than older, generic options such as sulfonylureas, which may affect the likelihood of their use, said Dr. McCoy, the Mayo Clinic researcher and lead author of the study on diabetes medication use by insurance type.

They analyzed 1.7 million individuals in a de-identified dataset (OptumLabs Data Warehouse) who were either privately insured or beneficiaries of Medicare Advantage, the private health plan alternative to fee-for-service Medicare.

After adjusting for race/ethnicity, baseline medications, age, gender, and other factors, odds of new medication use were significantly lower in the Medicare Advantage group, according to Dr. McCoy.

Odds ratios ranged from 0.61 (95% CI, 0.60-0.63) for DPP-4 inhibitors, to 0.45 (95% CI, 0.44-0.46) for GLP-1 receptor agonists, and to 0.31 (95% CI, 0.30-0.31) for SGLT2 inhibitors, she reported.

“This may be driven by affordability, because patients with Medicare Advantage plans are not able to access prescription savings cards (as compared to Medicare beneficiaries) and they also are more likely to have fixed incomes and not be able to afford the high costs of these drugs,” she said.

Dr. Elhussein reported no disclosures related to the research, while co-authors provided disclosures related to Abbott, Bigfoot Biomedical, Boehringer Ingelheim, Eli Lilly, MannKind, Medscape, Novo Nordisk, Sanofi US, and others. Dr McCoy likewise had no disclosures, while co-authors indicated disclosures related to Janssen Pharmaceuticals, the Centers for Medicare and Medicaid Services, and the U.S. Food and Drug Administration.

SOURCES: ADA 2020. Authors: McCoy R et al (38-OR), and Elhussein A, et al (37-OR).
 

Racial and socioeconomic disparities may be impeding access to newer diabetes medications among U.S. patients who may need them the most, according to researchers at the virtual annual scientific sessions of the American Diabetes Association.

Initiation of DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors was less likely among racial/ethnic minorities and Medicare Advantage beneficiaries in the retrospective analyses, leading the investigators to call for a better understanding of nonclinical factors that may be influencing treatment decisions.

Odds of new diabetes medication use were 55%-69% lower in patients in Medicare Advantage (MA) as compared to patients in commercial health plans, according to results of a separate study presented by Rozalina McCoy, MD, endocrinologist and researcher with Mayo Clinic, Rochester, Minn.

“The rates of use are increasing over time, but not enough in MA beneficiaries,” she said in her virtual presentation. “I think it really calls for more to be done to ensure access to and use of evidence based medications, by all people with type 2 diabetes.”

The likelihood of initiating a new diabetes drug was 29% lower among African Americans and 49% lower among Native Americans in a study of enrollees in the Look AHEAD (Action for Health in Diabetes) randomized trial, according to researcher Ahmed Elhussein, BMBCh, MPH, of the Johns Hopkins Bloomberg School of Public Health.

“This is particularly concerning, because they might have a greater need for these new diabetes medications, but reduced access,” Dr. Elhussein said in his presentation.

Disparities by race in diabetes drug use

The prevalence of type 2 diabetes in the United States is higher among racial and ethnic minorities, at about 12%-15%, versus about 7% in whites, according to Dr. Elhussein,

While the newer classes of diabetes medications have a lower risk of hyperglycemia and have cardiovascular and renal benefits, they also come at a higher cost, he added.

“This has created some concerns about access in particular for underserved groups,” he said in his presentation.

In their retrospective analysis, based on 4,892 patients enrolled in the Look AHEAD (Action for Health in Diabetes) randomized trial, Dr. Elhussein and coinvestigators identified 44% who had initiated a newer diabetes medication over a median follow-up of about 8 years.

They found black race was associated with significantly lower initiation of newer medications compared to whites, with a hazard ratio of 0.81 (95% confidence interval 0.80-0.94; P = 0.019), after adjustment for socioeconomic status.

New diabetes medication use was also significantly lower among American Indian/Alaskan Natives, with an HR of 0.51 and a confidence interval that did not include the null value of 1, according to the investigator.

No significant differences in new diabetes drug use were seen in Hispanics or those classified as other race/ethnicity, he added.

“We’d advocate for more study to try to understand what are the drivers of this disparity,” he said. “This would let us develop interventions that might help to increase access in these patient groups that might need them the most.”

Insurance type and diabetes drugs

Second-line medications, including GLP-1 receptor agonists and SGLT2 inhibitors, have “preferred” efficacy and side effect profiles, but are more costly than older, generic options such as sulfonylureas, which may affect the likelihood of their use, said Dr. McCoy, the Mayo Clinic researcher and lead author of the study on diabetes medication use by insurance type.

They analyzed 1.7 million individuals in a de-identified dataset (OptumLabs Data Warehouse) who were either privately insured or beneficiaries of Medicare Advantage, the private health plan alternative to fee-for-service Medicare.

After adjusting for race/ethnicity, baseline medications, age, gender, and other factors, odds of new medication use were significantly lower in the Medicare Advantage group, according to Dr. McCoy.

Odds ratios ranged from 0.61 (95% CI, 0.60-0.63) for DPP-4 inhibitors, to 0.45 (95% CI, 0.44-0.46) for GLP-1 receptor agonists, and to 0.31 (95% CI, 0.30-0.31) for SGLT2 inhibitors, she reported.

“This may be driven by affordability, because patients with Medicare Advantage plans are not able to access prescription savings cards (as compared to Medicare beneficiaries) and they also are more likely to have fixed incomes and not be able to afford the high costs of these drugs,” she said.

Dr. Elhussein reported no disclosures related to the research, while co-authors provided disclosures related to Abbott, Bigfoot Biomedical, Boehringer Ingelheim, Eli Lilly, MannKind, Medscape, Novo Nordisk, Sanofi US, and others. Dr McCoy likewise had no disclosures, while co-authors indicated disclosures related to Janssen Pharmaceuticals, the Centers for Medicare and Medicaid Services, and the U.S. Food and Drug Administration.

SOURCES: ADA 2020. Authors: McCoy R et al (38-OR), and Elhussein A, et al (37-OR).
 

Patients with type 2 diabetes treated with the SGLT2 inhibitor empagliflozin during the landmark EMPA-REG OUTCOME trial had a solidly reduced need to either start insulin treatment or intensify existing insulin treatment, compared with those given placebo, in a post-hoc analysis of the study’s findings.

Mitchel L. Zoler/Frontline Medical News

“Empagliflozin markedly and durably delayed the need for insulin initiation, and reduced the need for large dose increases in patients already using insulin,” Muthiah Vaduganathan, MD, said at the virtual annual scientific sessions of the American Diabetes Association.

The patients in the empagliflozin (Jardiance) arm of EMPA-REG OUTCOME had a 9% rate of initiating insulin treatment after 4 years in the study, compared with a 20% rate among patients who received placebo, a statistically significant 60% relative risk reduction. All patients in the trial continued on their background oral glucose-lowering medications.

Among the 48% of study patients who entered the study already using insulin as part of their usual regimen, 18% of those receiving empagliflozin required a significant increase in their insulin dosage (an increase of at least 20% from baseline) after 4 years. But among the control patients, 35% needed this level of insulin-dosage intensification, again a statistically significant difference that computed to a 58% relative reduction in the need for boosting the insulin dosage.

For both of these endpoints, the divergence between the empagliflozin and control arms became apparent within the first 6 months on treatment, and the between-group differences steadily increased during further follow-up. The analyses pooled the patients who received empagliflozin in the trial, which studied two different dosages of the drug.

Results add to the ‘risk and benefit conversation’

“This is one of the first studies to look at this question in a more granular fashion” in patients with type 2 diabetes receiving a drug from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class, said Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital in Boston. It provides “compelling” information to include when discussing oral diabetes-drug options with patients, he said in an interview.

Patients newly diagnosed with type 2 diabetes “often think about insulin” and their potential need to eventually start taking it, with the requirements it brings for training, monitoring, and drug delivery, along with the costs for insulin and glucose monitoring. “Patients are very attuned to potentially needing insulin and often ask about it. A reduced need for insulin will be an important part of the risk and benefit conversation” with patients about potential use of an SGLT2 inhibitor, he said.

Dr. Vaduganathan hypothesized that three factors could contribute to the impact of empagliflozin on insulin initiation and dosage level: a direct glycemic-control effect of the drug, the drug’s positive impact on overall well-being and function that could enhance patient movement, and the documented ability of treatment with empagliflozin and other drugs in its class to cut the rate of heart failure hospitalizations. This last feature is potentially relevant because insulin treatment often starts in patients with type 2 diabetes during a hospitalization, he noted.
 

Handelsman: Analysis shows no ‘spectacular effect’

The association of empagliflozin treatment with a reduced need for insulin seen in these data is consistent with expectations for patients with type 2 diabetes who receive an additional oral drug, commented Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of The Metabolic Institute of American in Tarzana, Calif. “In large part it has to do with patients on placebo having to get more insulin” because their additional oral-drug options were limited. Dr. Handelsman pointed out that during the period when the EMPA-REG OUTCOME trial ran, from 2010-2015, fewer oral drugs were available than today, and clinicians in the study were encouraged to treat patients to their goal glycemia level according to local guidelines. In addition to a modest but useful glycemic control effect from SGLT2 inhibitors that, on average, cut hemoglobin A_1c levels by about 0.5%, they may also give a small boost to insulin sensitivity that can also defer the need to add or increase insulin. The level of insulin-treatment deference reported in the new analysis was “not a spectacular effect” he said in an interview.

The EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) study followed 7,020 patients at 590 sites in 42 countries for a median of 3.1 years. The study’s primary endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction (excluding silent MI), or nonfatal stroke, and the results showed a statistically significant 14% relative risk reduction with empagliflozin treatment (N Engl J Med. 2015 Nov 26;373[22]:2117-28 ). The results also showed that 12 weeks into the study, before patients could receive any additional drugs, HbA_1c levels averaged 0.54%-0.6% lower among the empagliflozin-treated patients than those in the placebo arm, with smaller between-group differences maintained through the balance of the study. At entry, more than half the enrolled patients were routinely treated with metformin, and close to half were receiving a sulfonyurea agent.

The EMPA-REG OUTCOME results were also notable as showing for the first time that treatment with an SGLT2 inhibitor drug produced a substantial decrease in heart failure hospitalizations, incident heart failure, and progression of renal dysfunction, effects subsequently confirmed and also found for other agents in this drug class.

EMPA-REG OUTCOME was funded in part by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin (Jardiance). Dr. Vaduganathan has been an advisor to Boehringer Ingelheim and to Amgen, AstraZeneca, Baxter, Bayer, Cytokinetics, and Relypsa. Dr. Handelsman has been a consultant to several drug companies including Boehringer Ingelheim and Eli Lilly.

mzoler@mdedge.com

SOURCE: Vaduganathan M et al. ADA 2020, Abstract 30-OR.

Patients with type 2 diabetes treated with the SGLT2 inhibitor empagliflozin during the landmark EMPA-REG OUTCOME trial had a solidly reduced need to either start insulin treatment or intensify existing insulin treatment, compared with those given placebo, in a post-hoc analysis of the study’s findings.

Mitchel L. Zoler/Frontline Medical News

“Empagliflozin markedly and durably delayed the need for insulin initiation, and reduced the need for large dose increases in patients already using insulin,” Muthiah Vaduganathan, MD, said at the virtual annual scientific sessions of the American Diabetes Association.

The patients in the empagliflozin (Jardiance) arm of EMPA-REG OUTCOME had a 9% rate of initiating insulin treatment after 4 years in the study, compared with a 20% rate among patients who received placebo, a statistically significant 60% relative risk reduction. All patients in the trial continued on their background oral glucose-lowering medications.

Among the 48% of study patients who entered the study already using insulin as part of their usual regimen, 18% of those receiving empagliflozin required a significant increase in their insulin dosage (an increase of at least 20% from baseline) after 4 years. But among the control patients, 35% needed this level of insulin-dosage intensification, again a statistically significant difference that computed to a 58% relative reduction in the need for boosting the insulin dosage.

For both of these endpoints, the divergence between the empagliflozin and control arms became apparent within the first 6 months on treatment, and the between-group differences steadily increased during further follow-up. The analyses pooled the patients who received empagliflozin in the trial, which studied two different dosages of the drug.

Results add to the ‘risk and benefit conversation’

“This is one of the first studies to look at this question in a more granular fashion” in patients with type 2 diabetes receiving a drug from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class, said Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital in Boston. It provides “compelling” information to include when discussing oral diabetes-drug options with patients, he said in an interview.

Patients newly diagnosed with type 2 diabetes “often think about insulin” and their potential need to eventually start taking it, with the requirements it brings for training, monitoring, and drug delivery, along with the costs for insulin and glucose monitoring. “Patients are very attuned to potentially needing insulin and often ask about it. A reduced need for insulin will be an important part of the risk and benefit conversation” with patients about potential use of an SGLT2 inhibitor, he said.

Dr. Vaduganathan hypothesized that three factors could contribute to the impact of empagliflozin on insulin initiation and dosage level: a direct glycemic-control effect of the drug, the drug’s positive impact on overall well-being and function that could enhance patient movement, and the documented ability of treatment with empagliflozin and other drugs in its class to cut the rate of heart failure hospitalizations. This last feature is potentially relevant because insulin treatment often starts in patients with type 2 diabetes during a hospitalization, he noted.
 

Handelsman: Analysis shows no ‘spectacular effect’

The association of empagliflozin treatment with a reduced need for insulin seen in these data is consistent with expectations for patients with type 2 diabetes who receive an additional oral drug, commented Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of The Metabolic Institute of American in Tarzana, Calif. “In large part it has to do with patients on placebo having to get more insulin” because their additional oral-drug options were limited. Dr. Handelsman pointed out that during the period when the EMPA-REG OUTCOME trial ran, from 2010-2015, fewer oral drugs were available than today, and clinicians in the study were encouraged to treat patients to their goal glycemia level according to local guidelines. In addition to a modest but useful glycemic control effect from SGLT2 inhibitors that, on average, cut hemoglobin A_1c levels by about 0.5%, they may also give a small boost to insulin sensitivity that can also defer the need to add or increase insulin. The level of insulin-treatment deference reported in the new analysis was “not a spectacular effect” he said in an interview.

The EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) study followed 7,020 patients at 590 sites in 42 countries for a median of 3.1 years. The study’s primary endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction (excluding silent MI), or nonfatal stroke, and the results showed a statistically significant 14% relative risk reduction with empagliflozin treatment (N Engl J Med. 2015 Nov 26;373[22]:2117-28 ). The results also showed that 12 weeks into the study, before patients could receive any additional drugs, HbA_1c levels averaged 0.54%-0.6% lower among the empagliflozin-treated patients than those in the placebo arm, with smaller between-group differences maintained through the balance of the study. At entry, more than half the enrolled patients were routinely treated with metformin, and close to half were receiving a sulfonyurea agent.

The EMPA-REG OUTCOME results were also notable as showing for the first time that treatment with an SGLT2 inhibitor drug produced a substantial decrease in heart failure hospitalizations, incident heart failure, and progression of renal dysfunction, effects subsequently confirmed and also found for other agents in this drug class.

EMPA-REG OUTCOME was funded in part by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin (Jardiance). Dr. Vaduganathan has been an advisor to Boehringer Ingelheim and to Amgen, AstraZeneca, Baxter, Bayer, Cytokinetics, and Relypsa. Dr. Handelsman has been a consultant to several drug companies including Boehringer Ingelheim and Eli Lilly.

mzoler@mdedge.com

SOURCE: Vaduganathan M et al. ADA 2020, Abstract 30-OR.

Patients with type 2 diabetes treated with the SGLT2 inhibitor empagliflozin during the landmark EMPA-REG OUTCOME trial had a solidly reduced need to either start insulin treatment or intensify existing insulin treatment, compared with those given placebo, in a post-hoc analysis of the study’s findings.

Mitchel L. Zoler/Frontline Medical News

“Empagliflozin markedly and durably delayed the need for insulin initiation, and reduced the need for large dose increases in patients already using insulin,” Muthiah Vaduganathan, MD, said at the virtual annual scientific sessions of the American Diabetes Association.

The patients in the empagliflozin (Jardiance) arm of EMPA-REG OUTCOME had a 9% rate of initiating insulin treatment after 4 years in the study, compared with a 20% rate among patients who received placebo, a statistically significant 60% relative risk reduction. All patients in the trial continued on their background oral glucose-lowering medications.

Among the 48% of study patients who entered the study already using insulin as part of their usual regimen, 18% of those receiving empagliflozin required a significant increase in their insulin dosage (an increase of at least 20% from baseline) after 4 years. But among the control patients, 35% needed this level of insulin-dosage intensification, again a statistically significant difference that computed to a 58% relative reduction in the need for boosting the insulin dosage.

For both of these endpoints, the divergence between the empagliflozin and control arms became apparent within the first 6 months on treatment, and the between-group differences steadily increased during further follow-up. The analyses pooled the patients who received empagliflozin in the trial, which studied two different dosages of the drug.

Results add to the ‘risk and benefit conversation’

“This is one of the first studies to look at this question in a more granular fashion” in patients with type 2 diabetes receiving a drug from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class, said Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital in Boston. It provides “compelling” information to include when discussing oral diabetes-drug options with patients, he said in an interview.

Patients newly diagnosed with type 2 diabetes “often think about insulin” and their potential need to eventually start taking it, with the requirements it brings for training, monitoring, and drug delivery, along with the costs for insulin and glucose monitoring. “Patients are very attuned to potentially needing insulin and often ask about it. A reduced need for insulin will be an important part of the risk and benefit conversation” with patients about potential use of an SGLT2 inhibitor, he said.

Dr. Vaduganathan hypothesized that three factors could contribute to the impact of empagliflozin on insulin initiation and dosage level: a direct glycemic-control effect of the drug, the drug’s positive impact on overall well-being and function that could enhance patient movement, and the documented ability of treatment with empagliflozin and other drugs in its class to cut the rate of heart failure hospitalizations. This last feature is potentially relevant because insulin treatment often starts in patients with type 2 diabetes during a hospitalization, he noted.
 

Handelsman: Analysis shows no ‘spectacular effect’

The association of empagliflozin treatment with a reduced need for insulin seen in these data is consistent with expectations for patients with type 2 diabetes who receive an additional oral drug, commented Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of The Metabolic Institute of American in Tarzana, Calif. “In large part it has to do with patients on placebo having to get more insulin” because their additional oral-drug options were limited. Dr. Handelsman pointed out that during the period when the EMPA-REG OUTCOME trial ran, from 2010-2015, fewer oral drugs were available than today, and clinicians in the study were encouraged to treat patients to their goal glycemia level according to local guidelines. In addition to a modest but useful glycemic control effect from SGLT2 inhibitors that, on average, cut hemoglobin A_1c levels by about 0.5%, they may also give a small boost to insulin sensitivity that can also defer the need to add or increase insulin. The level of insulin-treatment deference reported in the new analysis was “not a spectacular effect” he said in an interview.

The EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) study followed 7,020 patients at 590 sites in 42 countries for a median of 3.1 years. The study’s primary endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction (excluding silent MI), or nonfatal stroke, and the results showed a statistically significant 14% relative risk reduction with empagliflozin treatment (N Engl J Med. 2015 Nov 26;373[22]:2117-28 ). The results also showed that 12 weeks into the study, before patients could receive any additional drugs, HbA_1c levels averaged 0.54%-0.6% lower among the empagliflozin-treated patients than those in the placebo arm, with smaller between-group differences maintained through the balance of the study. At entry, more than half the enrolled patients were routinely treated with metformin, and close to half were receiving a sulfonyurea agent.

The EMPA-REG OUTCOME results were also notable as showing for the first time that treatment with an SGLT2 inhibitor drug produced a substantial decrease in heart failure hospitalizations, incident heart failure, and progression of renal dysfunction, effects subsequently confirmed and also found for other agents in this drug class.

EMPA-REG OUTCOME was funded in part by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin (Jardiance). Dr. Vaduganathan has been an advisor to Boehringer Ingelheim and to Amgen, AstraZeneca, Baxter, Bayer, Cytokinetics, and Relypsa. Dr. Handelsman has been a consultant to several drug companies including Boehringer Ingelheim and Eli Lilly.

mzoler@mdedge.com

SOURCE: Vaduganathan M et al. ADA 2020, Abstract 30-OR.

In its first media briefing on coronavirus in more than 3 months, the Centers for Disease Control and Prevention (CDC) warned that the COVID-19 pandemic is not over, and large gatherings pose a high risk for COVID-19 transmission.

Robert Redfield, MD, Director, CDC, and Jay C. Butler, MD, Deputy Director of Infectious Diseases and COVID-19 Response Incident Manager, CDC, discussed two new sets of CDC guidance on deciding to go out and attending group gatherings.

“We recognize that we’re all getting tired of staying at home; people long for the life that they had back in December, and as we head into the summer months, we know that Americans will be looking forward to reconnecting with family and friends and being able to attend events, and we want that to occur as safely as possible,” Butler said.

“Our recommendations evolved based on new information that becomes available, but it continues to be extremely important that we embrace the recommendations of social distancing, handwashing, and wearing a face covering when we’re in public as some of the key defenses that we have against this virus,” Redfield explained.

“The pandemic is not over and it’s important to recognize that. While COVID-19 is still making headlines everywhere, we know the pandemic hasn’t affected everyone everywhere in the same way,” Butler said.

He noted that it is important to prepare for next fall and winter, when we can expect influenza season to complicate matters. “If anything, we must be overly-prepared for what we might face later this year,” he continued, adding that it is important to get vaccinated against influenza. “[F]lu and COVID-19 could be circulating together as we move into the fall and winter months,” he concluded.

Americans Mostly Following Guidelines

The agency also presented data from an article published online June 12 in Morbidity and Mortality Weekly Report that “underscores the fact that American people have taken mitigation efforts seriously…and it demonstrates our collective spirit in responding to the pandemic,” Butler said.

In it, the researchers describe representative panel surveys conducted among 4042 adults aged 18 years or older in New York City and Los Angeles — the two most populous cities in the United States — and “broadly across the United States” during May 5 to May 12, 2020.

Most respondents supported stay-at-home orders and nonessential business closures (United States, 79.5%; New York City, 86.7%; Los Angeles, 81.5%) and always or often wore cloth face coverings in public (United States, 74.1%; New York City, 89.6%; Los Angeles, 89.8%). Respondents also agreed that nonessential workers should remain at home (United States, 67.3%; New York City, 76.6%; Los Angeles, 69.1%), report Mark É. Czeisler, from Monash University and Austin Health, both in Melbourne, Australia, and colleagues.

There was wide support with public health guidelines: more than 87% of individuals in each area agreed that individuals should keep six feet of distance between themselves and others, and more than 82% in each area said that people should limit gatherings to fewer than 10 individuals.

At the time the survey was conducted, most were against indoor dining at restaurants (United States, 66.6%; New York City, 81.5%; Los Angeles, 71.8%).

Adherence “Widespread,” Survey Finds

Most respondents said they were adhering to COVID-19 mitigation guidance, including self-isolating (United States, 77.3%; New York City, 84.6%; Los Angeles, 83.0%) and “always or often” kept at least six feet between themselves and others (New York City, 85.7%; Los Angeles, 82.6%).

More than 85% of respondents in each of the three cohorts said they always or often avoided groups of 10 or more individuals.

About 90% of respondents said they had been in a public area during the last week, with 74.1% of those saying they always or often covered their face in public; respondents in New York City (89.6%) and Los Angeles (89.8%) had higher percentages of this behavior compared with respondents from the United States overall.

Most respondents felt that restrictions in their state were balanced or too lax (United States, 84.3%; New York City, 89.7%; Los Angeles, 79.7%) and said they would feel unsafe if restrictions were eased nationwide at that time (United States, 74.3%; New York City, 81.5%; Los Angeles, 73.4%). However, some individuals who said they would feel unsafe still wanted community mitigation strategies eased and were willing to accept risks resulting from lifting restrictions (United States, 17.1%; New York City, 12.6%; Los Angeles, 12.7%).

“Reported prevalence of self-isolation and feeling safe if community mitigation strategies were lifted differed significantly by age, employment status, and essential worker status among adults in the U.S. survey cohort,” the authors write.

Reports of self-isolation were highest among persons aged 18 to 24 years (92.3%) and lowest among those aged 45 to 54 years (71.5%). Yet, young adults aged 18 to 24 years (43.1%) were more than twice as likely to say they would feel safe if community mitigation strategies were eased, compared with adults aged 65 years or older (19.2%).

Almost half (47.2%) of employed respondents in the US cohort were essential workers; essential workers were “significantly less likely” to report self-isolating when compared with nonessential workers (63.1% vs 80.6%). Some 37.7% of essential workers said they would feel safe if community mitigation strategies were eased, compared with 23.7% of nonessential workers.

“Respondents who were male, employed, or essential workers were significantly more likely to report having been in public areas in the past week. Among respondents who had been in public areas during the preceding week, significantly higher percentages of women, adults aged ≥ 65 years, retired persons, and those living in urban areas reported wearing cloth face coverings,” the authors explain.

The findings are subject to several limitations, including self-reporting and the fact that some respondents may have known someone who tested positive for COVID-19 or died from it, the authors note. Respondents were not representative of the US population and the findings may not be generalizable.


This article first appeared on Medscape.com.

In its first media briefing on coronavirus in more than 3 months, the Centers for Disease Control and Prevention (CDC) warned that the COVID-19 pandemic is not over, and large gatherings pose a high risk for COVID-19 transmission.

Robert Redfield, MD, Director, CDC, and Jay C. Butler, MD, Deputy Director of Infectious Diseases and COVID-19 Response Incident Manager, CDC, discussed two new sets of CDC guidance on deciding to go out and attending group gatherings.

“We recognize that we’re all getting tired of staying at home; people long for the life that they had back in December, and as we head into the summer months, we know that Americans will be looking forward to reconnecting with family and friends and being able to attend events, and we want that to occur as safely as possible,” Butler said.

“Our recommendations evolved based on new information that becomes available, but it continues to be extremely important that we embrace the recommendations of social distancing, handwashing, and wearing a face covering when we’re in public as some of the key defenses that we have against this virus,” Redfield explained.

“The pandemic is not over and it’s important to recognize that. While COVID-19 is still making headlines everywhere, we know the pandemic hasn’t affected everyone everywhere in the same way,” Butler said.

He noted that it is important to prepare for next fall and winter, when we can expect influenza season to complicate matters. “If anything, we must be overly-prepared for what we might face later this year,” he continued, adding that it is important to get vaccinated against influenza. “[F]lu and COVID-19 could be circulating together as we move into the fall and winter months,” he concluded.

Americans Mostly Following Guidelines

The agency also presented data from an article published online June 12 in Morbidity and Mortality Weekly Report that “underscores the fact that American people have taken mitigation efforts seriously…and it demonstrates our collective spirit in responding to the pandemic,” Butler said.

In it, the researchers describe representative panel surveys conducted among 4042 adults aged 18 years or older in New York City and Los Angeles — the two most populous cities in the United States — and “broadly across the United States” during May 5 to May 12, 2020.

Most respondents supported stay-at-home orders and nonessential business closures (United States, 79.5%; New York City, 86.7%; Los Angeles, 81.5%) and always or often wore cloth face coverings in public (United States, 74.1%; New York City, 89.6%; Los Angeles, 89.8%). Respondents also agreed that nonessential workers should remain at home (United States, 67.3%; New York City, 76.6%; Los Angeles, 69.1%), report Mark É. Czeisler, from Monash University and Austin Health, both in Melbourne, Australia, and colleagues.

There was wide support with public health guidelines: more than 87% of individuals in each area agreed that individuals should keep six feet of distance between themselves and others, and more than 82% in each area said that people should limit gatherings to fewer than 10 individuals.

At the time the survey was conducted, most were against indoor dining at restaurants (United States, 66.6%; New York City, 81.5%; Los Angeles, 71.8%).

Adherence “Widespread,” Survey Finds

Most respondents said they were adhering to COVID-19 mitigation guidance, including self-isolating (United States, 77.3%; New York City, 84.6%; Los Angeles, 83.0%) and “always or often” kept at least six feet between themselves and others (New York City, 85.7%; Los Angeles, 82.6%).

More than 85% of respondents in each of the three cohorts said they always or often avoided groups of 10 or more individuals.

About 90% of respondents said they had been in a public area during the last week, with 74.1% of those saying they always or often covered their face in public; respondents in New York City (89.6%) and Los Angeles (89.8%) had higher percentages of this behavior compared with respondents from the United States overall.

Most respondents felt that restrictions in their state were balanced or too lax (United States, 84.3%; New York City, 89.7%; Los Angeles, 79.7%) and said they would feel unsafe if restrictions were eased nationwide at that time (United States, 74.3%; New York City, 81.5%; Los Angeles, 73.4%). However, some individuals who said they would feel unsafe still wanted community mitigation strategies eased and were willing to accept risks resulting from lifting restrictions (United States, 17.1%; New York City, 12.6%; Los Angeles, 12.7%).

“Reported prevalence of self-isolation and feeling safe if community mitigation strategies were lifted differed significantly by age, employment status, and essential worker status among adults in the U.S. survey cohort,” the authors write.

Reports of self-isolation were highest among persons aged 18 to 24 years (92.3%) and lowest among those aged 45 to 54 years (71.5%). Yet, young adults aged 18 to 24 years (43.1%) were more than twice as likely to say they would feel safe if community mitigation strategies were eased, compared with adults aged 65 years or older (19.2%).

Almost half (47.2%) of employed respondents in the US cohort were essential workers; essential workers were “significantly less likely” to report self-isolating when compared with nonessential workers (63.1% vs 80.6%). Some 37.7% of essential workers said they would feel safe if community mitigation strategies were eased, compared with 23.7% of nonessential workers.

“Respondents who were male, employed, or essential workers were significantly more likely to report having been in public areas in the past week. Among respondents who had been in public areas during the preceding week, significantly higher percentages of women, adults aged ≥ 65 years, retired persons, and those living in urban areas reported wearing cloth face coverings,” the authors explain.

The findings are subject to several limitations, including self-reporting and the fact that some respondents may have known someone who tested positive for COVID-19 or died from it, the authors note. Respondents were not representative of the US population and the findings may not be generalizable.


This article first appeared on Medscape.com.

In its first media briefing on coronavirus in more than 3 months, the Centers for Disease Control and Prevention (CDC) warned that the COVID-19 pandemic is not over, and large gatherings pose a high risk for COVID-19 transmission.

Robert Redfield, MD, Director, CDC, and Jay C. Butler, MD, Deputy Director of Infectious Diseases and COVID-19 Response Incident Manager, CDC, discussed two new sets of CDC guidance on deciding to go out and attending group gatherings.

“We recognize that we’re all getting tired of staying at home; people long for the life that they had back in December, and as we head into the summer months, we know that Americans will be looking forward to reconnecting with family and friends and being able to attend events, and we want that to occur as safely as possible,” Butler said.

“Our recommendations evolved based on new information that becomes available, but it continues to be extremely important that we embrace the recommendations of social distancing, handwashing, and wearing a face covering when we’re in public as some of the key defenses that we have against this virus,” Redfield explained.

“The pandemic is not over and it’s important to recognize that. While COVID-19 is still making headlines everywhere, we know the pandemic hasn’t affected everyone everywhere in the same way,” Butler said.

He noted that it is important to prepare for next fall and winter, when we can expect influenza season to complicate matters. “If anything, we must be overly-prepared for what we might face later this year,” he continued, adding that it is important to get vaccinated against influenza. “[F]lu and COVID-19 could be circulating together as we move into the fall and winter months,” he concluded.

Americans Mostly Following Guidelines

The agency also presented data from an article published online June 12 in Morbidity and Mortality Weekly Report that “underscores the fact that American people have taken mitigation efforts seriously…and it demonstrates our collective spirit in responding to the pandemic,” Butler said.

In it, the researchers describe representative panel surveys conducted among 4042 adults aged 18 years or older in New York City and Los Angeles — the two most populous cities in the United States — and “broadly across the United States” during May 5 to May 12, 2020.

Most respondents supported stay-at-home orders and nonessential business closures (United States, 79.5%; New York City, 86.7%; Los Angeles, 81.5%) and always or often wore cloth face coverings in public (United States, 74.1%; New York City, 89.6%; Los Angeles, 89.8%). Respondents also agreed that nonessential workers should remain at home (United States, 67.3%; New York City, 76.6%; Los Angeles, 69.1%), report Mark É. Czeisler, from Monash University and Austin Health, both in Melbourne, Australia, and colleagues.

There was wide support with public health guidelines: more than 87% of individuals in each area agreed that individuals should keep six feet of distance between themselves and others, and more than 82% in each area said that people should limit gatherings to fewer than 10 individuals.

At the time the survey was conducted, most were against indoor dining at restaurants (United States, 66.6%; New York City, 81.5%; Los Angeles, 71.8%).

Adherence “Widespread,” Survey Finds

Most respondents said they were adhering to COVID-19 mitigation guidance, including self-isolating (United States, 77.3%; New York City, 84.6%; Los Angeles, 83.0%) and “always or often” kept at least six feet between themselves and others (New York City, 85.7%; Los Angeles, 82.6%).

More than 85% of respondents in each of the three cohorts said they always or often avoided groups of 10 or more individuals.

About 90% of respondents said they had been in a public area during the last week, with 74.1% of those saying they always or often covered their face in public; respondents in New York City (89.6%) and Los Angeles (89.8%) had higher percentages of this behavior compared with respondents from the United States overall.

Most respondents felt that restrictions in their state were balanced or too lax (United States, 84.3%; New York City, 89.7%; Los Angeles, 79.7%) and said they would feel unsafe if restrictions were eased nationwide at that time (United States, 74.3%; New York City, 81.5%; Los Angeles, 73.4%). However, some individuals who said they would feel unsafe still wanted community mitigation strategies eased and were willing to accept risks resulting from lifting restrictions (United States, 17.1%; New York City, 12.6%; Los Angeles, 12.7%).

“Reported prevalence of self-isolation and feeling safe if community mitigation strategies were lifted differed significantly by age, employment status, and essential worker status among adults in the U.S. survey cohort,” the authors write.

Reports of self-isolation were highest among persons aged 18 to 24 years (92.3%) and lowest among those aged 45 to 54 years (71.5%). Yet, young adults aged 18 to 24 years (43.1%) were more than twice as likely to say they would feel safe if community mitigation strategies were eased, compared with adults aged 65 years or older (19.2%).

Almost half (47.2%) of employed respondents in the US cohort were essential workers; essential workers were “significantly less likely” to report self-isolating when compared with nonessential workers (63.1% vs 80.6%). Some 37.7% of essential workers said they would feel safe if community mitigation strategies were eased, compared with 23.7% of nonessential workers.

“Respondents who were male, employed, or essential workers were significantly more likely to report having been in public areas in the past week. Among respondents who had been in public areas during the preceding week, significantly higher percentages of women, adults aged ≥ 65 years, retired persons, and those living in urban areas reported wearing cloth face coverings,” the authors explain.

The findings are subject to several limitations, including self-reporting and the fact that some respondents may have known someone who tested positive for COVID-19 or died from it, the authors note. Respondents were not representative of the US population and the findings may not be generalizable.


This article first appeared on Medscape.com.