Pharmacology

Sometimes we get what we pay for. Other times we pay too much. 

That’s the message of a study published in Annals of Internal Medicine, which finds that a generic maintenance inhaler is as effective at managing symptoms of chronic obstructive pulmonary disorder (COPD) as a pricier branded alternative. 

In 2019, the Food and Drug Administration approved Wixela Inhub (the combination corticosteroid/long-acting beta² adrenergic agonist fluticasone-salmeterol; Viatris) as a generic dry powder inhaler for managing symptoms of COPD. This approval was based on evidence of the generic’s effectiveness against asthma, although COPD also was on the product label. The study authors compared Wixela’s effectiveness in controlling symptoms of COPD with that of the brand name inhaler Advair Diskus (fluticasone-salmeterol; GlaxoSmithKline), which uses the same active ingredients.

The result: “The generic looks to be as safe and effective as the brand name. I don’t see a clinical reason why one would ever need to get the brand name over the generic version,” said study author William Feldman, MD, DPhil, MPH, a health services researcher and pulmonologist at Harvard Medical School and Brigham and Women’s Hospital, both in Boston.
 

Same types of patients, different inhalers, same outcomes

Dr. Feldman and colleagues compared the medical records of 10,000 patients with COPD who began using the branded inhaler to the records of another 10,000 patients with COPD who opted for the generic alternative. Participants in the two groups were evenly matched by age, sex, race, and ethnicity, region, severity of COPD, and presence of other comorbidities, according to the researchers. Participants were all older than age 40, and the average age in both groups was 72 years.

The researchers looked for a difference in a first episode of a moderate exacerbation of COPD, defined as requiring a course of prednisone for 5-14 days. They also looked for cases of severe COPD exacerbation requiring hospitalization in the year after people began using either the generic or brand name inhaler. And they looked for differences across 1 year in rates of hospitalization for pneumonia.

For none of those outcomes, however, did the type of inhaler appear to matter. Compared with the brand-name drug, using the generic was associated with nearly identical rates of moderate or severe COPD exacerbation (hazard ratio, 0.97; 95% confidence interval, 0.90-1.04. The same was true for the proportion of people who went to the hospital for pneumonia at least once (HR, 0.99; 95% CI, 0.86-1.15).

“To get through the FDA as an interchangeable generic, the generic firms have to show that their product can be used in just the same way as the brand-name version,” Dr. Feldman said, which may explain why the generic and brand-name versions of the inhaler performed so similarly.

Dr. Feldman cautioned that the price savings for patients who opt for the generic over the branded product are hard to determine, given the vagaries of different insurance plans and potential rebates when using the branded project. As a general matter, having a single generic competitor will not lower costs much, Dr. Feldman noted, pointing to 2017 research from Harvard that found a profusion of generic competitors is needed to significantly lower health care costs.

“I don’t want to in any way underestimate the importance of getting that first generic onto the market, because it sets the stage for future generics,” Dr. Feldman said.  

“There are very few generic options for patients with COPD,” said Surya Bhatt, MD, director of the Pulmonary Function and Exercise Physiology Lab at the University of Alabama at Birmingham. Even the rescue inhalers that people with COPD use to manage acute episodes of the condition are usually branded at this time, Dr. Bhatt noted, with few generic options.*

“The results are quite compelling,” said Dr. Bhatt, who was not involved in the research. Although the trial was not randomized, he commended the researchers for stratifying participants in the two groups to be as comparable as possible.

Dr. Bhatt noted that the FDA’s 2019 approval – given that the agency requires bioequivalence studies between branded and generic products – was enough to cause him to begin prescribing the generic inhaler. The fact that this approval was based on asthma but not also COPD is not a concern.

“There are so many similarities between asthma, COPD, and some obstructive lung diseases,” Dr. Bhatt noted.

In his experience, the only time someone with COPD continues using the branded inhaler – now that a potentially cheaper generic is available – is when their insurance plan makes their out-of-pocket cost minimal. Otherwise, brand loyalty does not exist.

“Patients are generally okay with being on a generic for inhalers, just because of the high cost,” Dr. Bhatt said.

The study was primarily supported by the National Heart, Lung, and Blood Institute. Dr. Feldman reported funding from Arnold Ventures, the Commonwealth Fund, and the FDA, and consulting relationships with Alosa Health and Aetion. Dr. Bhatt reported no relevant financial relationships.

*Correction, 8/16/23: An earlier version of this article mischaracterized Dr. Bhatt's comments on the availability of generic options.

A version of this article first appeared on Medscape.com.

Sometimes we get what we pay for. Other times we pay too much. 

That’s the message of a study published in Annals of Internal Medicine, which finds that a generic maintenance inhaler is as effective at managing symptoms of chronic obstructive pulmonary disorder (COPD) as a pricier branded alternative. 

In 2019, the Food and Drug Administration approved Wixela Inhub (the combination corticosteroid/long-acting beta² adrenergic agonist fluticasone-salmeterol; Viatris) as a generic dry powder inhaler for managing symptoms of COPD. This approval was based on evidence of the generic’s effectiveness against asthma, although COPD also was on the product label. The study authors compared Wixela’s effectiveness in controlling symptoms of COPD with that of the brand name inhaler Advair Diskus (fluticasone-salmeterol; GlaxoSmithKline), which uses the same active ingredients.

The result: “The generic looks to be as safe and effective as the brand name. I don’t see a clinical reason why one would ever need to get the brand name over the generic version,” said study author William Feldman, MD, DPhil, MPH, a health services researcher and pulmonologist at Harvard Medical School and Brigham and Women’s Hospital, both in Boston.
 

Same types of patients, different inhalers, same outcomes

Dr. Feldman and colleagues compared the medical records of 10,000 patients with COPD who began using the branded inhaler to the records of another 10,000 patients with COPD who opted for the generic alternative. Participants in the two groups were evenly matched by age, sex, race, and ethnicity, region, severity of COPD, and presence of other comorbidities, according to the researchers. Participants were all older than age 40, and the average age in both groups was 72 years.

The researchers looked for a difference in a first episode of a moderate exacerbation of COPD, defined as requiring a course of prednisone for 5-14 days. They also looked for cases of severe COPD exacerbation requiring hospitalization in the year after people began using either the generic or brand name inhaler. And they looked for differences across 1 year in rates of hospitalization for pneumonia.

For none of those outcomes, however, did the type of inhaler appear to matter. Compared with the brand-name drug, using the generic was associated with nearly identical rates of moderate or severe COPD exacerbation (hazard ratio, 0.97; 95% confidence interval, 0.90-1.04. The same was true for the proportion of people who went to the hospital for pneumonia at least once (HR, 0.99; 95% CI, 0.86-1.15).

“To get through the FDA as an interchangeable generic, the generic firms have to show that their product can be used in just the same way as the brand-name version,” Dr. Feldman said, which may explain why the generic and brand-name versions of the inhaler performed so similarly.

Dr. Feldman cautioned that the price savings for patients who opt for the generic over the branded product are hard to determine, given the vagaries of different insurance plans and potential rebates when using the branded project. As a general matter, having a single generic competitor will not lower costs much, Dr. Feldman noted, pointing to 2017 research from Harvard that found a profusion of generic competitors is needed to significantly lower health care costs.

“I don’t want to in any way underestimate the importance of getting that first generic onto the market, because it sets the stage for future generics,” Dr. Feldman said.  

“There are very few generic options for patients with COPD,” said Surya Bhatt, MD, director of the Pulmonary Function and Exercise Physiology Lab at the University of Alabama at Birmingham. Even the rescue inhalers that people with COPD use to manage acute episodes of the condition are usually branded at this time, Dr. Bhatt noted, with few generic options.*

“The results are quite compelling,” said Dr. Bhatt, who was not involved in the research. Although the trial was not randomized, he commended the researchers for stratifying participants in the two groups to be as comparable as possible.

Dr. Bhatt noted that the FDA’s 2019 approval – given that the agency requires bioequivalence studies between branded and generic products – was enough to cause him to begin prescribing the generic inhaler. The fact that this approval was based on asthma but not also COPD is not a concern.

“There are so many similarities between asthma, COPD, and some obstructive lung diseases,” Dr. Bhatt noted.

In his experience, the only time someone with COPD continues using the branded inhaler – now that a potentially cheaper generic is available – is when their insurance plan makes their out-of-pocket cost minimal. Otherwise, brand loyalty does not exist.

“Patients are generally okay with being on a generic for inhalers, just because of the high cost,” Dr. Bhatt said.

The study was primarily supported by the National Heart, Lung, and Blood Institute. Dr. Feldman reported funding from Arnold Ventures, the Commonwealth Fund, and the FDA, and consulting relationships with Alosa Health and Aetion. Dr. Bhatt reported no relevant financial relationships.

*Correction, 8/16/23: An earlier version of this article mischaracterized Dr. Bhatt's comments on the availability of generic options.

A version of this article first appeared on Medscape.com.

Sometimes we get what we pay for. Other times we pay too much. 

That’s the message of a study published in Annals of Internal Medicine, which finds that a generic maintenance inhaler is as effective at managing symptoms of chronic obstructive pulmonary disorder (COPD) as a pricier branded alternative. 

In 2019, the Food and Drug Administration approved Wixela Inhub (the combination corticosteroid/long-acting beta² adrenergic agonist fluticasone-salmeterol; Viatris) as a generic dry powder inhaler for managing symptoms of COPD. This approval was based on evidence of the generic’s effectiveness against asthma, although COPD also was on the product label. The study authors compared Wixela’s effectiveness in controlling symptoms of COPD with that of the brand name inhaler Advair Diskus (fluticasone-salmeterol; GlaxoSmithKline), which uses the same active ingredients.

The result: “The generic looks to be as safe and effective as the brand name. I don’t see a clinical reason why one would ever need to get the brand name over the generic version,” said study author William Feldman, MD, DPhil, MPH, a health services researcher and pulmonologist at Harvard Medical School and Brigham and Women’s Hospital, both in Boston.
 

Same types of patients, different inhalers, same outcomes

Dr. Feldman and colleagues compared the medical records of 10,000 patients with COPD who began using the branded inhaler to the records of another 10,000 patients with COPD who opted for the generic alternative. Participants in the two groups were evenly matched by age, sex, race, and ethnicity, region, severity of COPD, and presence of other comorbidities, according to the researchers. Participants were all older than age 40, and the average age in both groups was 72 years.

The researchers looked for a difference in a first episode of a moderate exacerbation of COPD, defined as requiring a course of prednisone for 5-14 days. They also looked for cases of severe COPD exacerbation requiring hospitalization in the year after people began using either the generic or brand name inhaler. And they looked for differences across 1 year in rates of hospitalization for pneumonia.

For none of those outcomes, however, did the type of inhaler appear to matter. Compared with the brand-name drug, using the generic was associated with nearly identical rates of moderate or severe COPD exacerbation (hazard ratio, 0.97; 95% confidence interval, 0.90-1.04. The same was true for the proportion of people who went to the hospital for pneumonia at least once (HR, 0.99; 95% CI, 0.86-1.15).

“To get through the FDA as an interchangeable generic, the generic firms have to show that their product can be used in just the same way as the brand-name version,” Dr. Feldman said, which may explain why the generic and brand-name versions of the inhaler performed so similarly.

Dr. Feldman cautioned that the price savings for patients who opt for the generic over the branded product are hard to determine, given the vagaries of different insurance plans and potential rebates when using the branded project. As a general matter, having a single generic competitor will not lower costs much, Dr. Feldman noted, pointing to 2017 research from Harvard that found a profusion of generic competitors is needed to significantly lower health care costs.

“I don’t want to in any way underestimate the importance of getting that first generic onto the market, because it sets the stage for future generics,” Dr. Feldman said.  

“There are very few generic options for patients with COPD,” said Surya Bhatt, MD, director of the Pulmonary Function and Exercise Physiology Lab at the University of Alabama at Birmingham. Even the rescue inhalers that people with COPD use to manage acute episodes of the condition are usually branded at this time, Dr. Bhatt noted, with few generic options.*

“The results are quite compelling,” said Dr. Bhatt, who was not involved in the research. Although the trial was not randomized, he commended the researchers for stratifying participants in the two groups to be as comparable as possible.

Dr. Bhatt noted that the FDA’s 2019 approval – given that the agency requires bioequivalence studies between branded and generic products – was enough to cause him to begin prescribing the generic inhaler. The fact that this approval was based on asthma but not also COPD is not a concern.

“There are so many similarities between asthma, COPD, and some obstructive lung diseases,” Dr. Bhatt noted.

In his experience, the only time someone with COPD continues using the branded inhaler – now that a potentially cheaper generic is available – is when their insurance plan makes their out-of-pocket cost minimal. Otherwise, brand loyalty does not exist.

“Patients are generally okay with being on a generic for inhalers, just because of the high cost,” Dr. Bhatt said.

The study was primarily supported by the National Heart, Lung, and Blood Institute. Dr. Feldman reported funding from Arnold Ventures, the Commonwealth Fund, and the FDA, and consulting relationships with Alosa Health and Aetion. Dr. Bhatt reported no relevant financial relationships.

*Correction, 8/16/23: An earlier version of this article mischaracterized Dr. Bhatt's comments on the availability of generic options.

A version of this article first appeared on Medscape.com.

Ancestry was a significant predictor of response to lithium by adults with bipolar disorder (BPD), based on data from 172 individuals.

Lithium remains the first-line treatment for BPD, but clinical improvement occurs in less than one-third of patients, and factors that might affect response, especially genetic factors, have not been well studied, wrote Ana M. Díaz-Zuluaga, MD, of University of Antioquia, Medellín, Colombia, and colleagues.

Previous genetic research identified four linked single nucleotide polymorphisms (SNPs) in a single locus on chromosome 21 that were associated with lithium response, but the study was limited to individuals with European and Asian ancestry, the researchers said.

In a study published in the Journal of Affective Disorders, the researchers identified 172 adults aged 18 and older with a diagnosis of BPD I or II based on the DSM-IV-TR criteria. Participants had been taking lithium continuously for at least 6 months. Lithium response was defined using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with BD, also known as the Alda scale. Total Alda scale scores of 7 or higher indicated a responder phenotype; scores less than 7 were considered nonresponders.

Ancestry was determined using DNA samples and the software Structure Version 2.2, and participants were classified as Amerindian, African, or European.

The overall response rate to lithium was 15.11% (26 of 172 patients). In a univariate analysis, no significant differences emerged between responders and nonresponders in demographics or clinical characteristics. However, patients responsive to lithium were significantly less likely of African ancestry, compared with nonresponders (0.1 vs. 0.2, P = .005) and more likely of European ancestry (0.5 vs. 0.3, P = .024), and had fewer depressive episodes (2 vs. 3.9, P = .002). The difference in responders vs. nonresponders of Amerindian ancestry was not statistically significant (0.4 vs. 0.5, P = .204).

The researchers then used machine learning based on Advanced Recursive Partitioning Approaches (ARPAs) to create classification trees with and without ancestry components for predicting response to lithium. “Variable importance analysis shows that the most important predictor is the probability of Amerindian ancestry component, followed by the Amerindian and European ancestral components individual variances, and then by the African and European ancestry components,” the researchers wrote.

Without the ancestry component, the sensitivity and specificity for predicting a treatment response to lithium were 50% and 94.5% respectively, with an area under the curve of 72.2%.

“However, when ancestral components are included in the model, the sensitivity and specificity are 93 % and 84 %, respectively,” with an AUC of 89.2%, the researchers said.

Clinical predictors of treatment response included disease duration, number of depressive episodes, total number of affective episodes, and number of manic episodes.

The findings were limited by several factors including the cross-sectional design and potential impact of other psychotropic drugs, the researchers noted. A replication of the study in an independent dataset is needed to validate the findings, they said.

However, the study is the first known to explore the effect of ancestry on bipolar patients’ response to lithium, and suggests that ancestry components have potential predictive value in the clinical setting that could support a more personalized approach to treatment, the researchers said.

The study was supported by PRISMA U.T., Colciencias, Invitación 990 del 3 de Agosto de 2017, Código 111577757629, Contrato 781 de 2017; Convocatoria Programática Ciencias de la Salud 2014-2015 CODI-UdeA, and Convocatoria N.727-2015 Doctorados Nacionales, Colciencias, 2015. The researchers had no financial conflicts to disclose.

Ancestry was a significant predictor of response to lithium by adults with bipolar disorder (BPD), based on data from 172 individuals.

Lithium remains the first-line treatment for BPD, but clinical improvement occurs in less than one-third of patients, and factors that might affect response, especially genetic factors, have not been well studied, wrote Ana M. Díaz-Zuluaga, MD, of University of Antioquia, Medellín, Colombia, and colleagues.

Previous genetic research identified four linked single nucleotide polymorphisms (SNPs) in a single locus on chromosome 21 that were associated with lithium response, but the study was limited to individuals with European and Asian ancestry, the researchers said.

In a study published in the Journal of Affective Disorders, the researchers identified 172 adults aged 18 and older with a diagnosis of BPD I or II based on the DSM-IV-TR criteria. Participants had been taking lithium continuously for at least 6 months. Lithium response was defined using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with BD, also known as the Alda scale. Total Alda scale scores of 7 or higher indicated a responder phenotype; scores less than 7 were considered nonresponders.

Ancestry was determined using DNA samples and the software Structure Version 2.2, and participants were classified as Amerindian, African, or European.

The overall response rate to lithium was 15.11% (26 of 172 patients). In a univariate analysis, no significant differences emerged between responders and nonresponders in demographics or clinical characteristics. However, patients responsive to lithium were significantly less likely of African ancestry, compared with nonresponders (0.1 vs. 0.2, P = .005) and more likely of European ancestry (0.5 vs. 0.3, P = .024), and had fewer depressive episodes (2 vs. 3.9, P = .002). The difference in responders vs. nonresponders of Amerindian ancestry was not statistically significant (0.4 vs. 0.5, P = .204).

The researchers then used machine learning based on Advanced Recursive Partitioning Approaches (ARPAs) to create classification trees with and without ancestry components for predicting response to lithium. “Variable importance analysis shows that the most important predictor is the probability of Amerindian ancestry component, followed by the Amerindian and European ancestral components individual variances, and then by the African and European ancestry components,” the researchers wrote.

Without the ancestry component, the sensitivity and specificity for predicting a treatment response to lithium were 50% and 94.5% respectively, with an area under the curve of 72.2%.

“However, when ancestral components are included in the model, the sensitivity and specificity are 93 % and 84 %, respectively,” with an AUC of 89.2%, the researchers said.

Clinical predictors of treatment response included disease duration, number of depressive episodes, total number of affective episodes, and number of manic episodes.

The findings were limited by several factors including the cross-sectional design and potential impact of other psychotropic drugs, the researchers noted. A replication of the study in an independent dataset is needed to validate the findings, they said.

However, the study is the first known to explore the effect of ancestry on bipolar patients’ response to lithium, and suggests that ancestry components have potential predictive value in the clinical setting that could support a more personalized approach to treatment, the researchers said.

The study was supported by PRISMA U.T., Colciencias, Invitación 990 del 3 de Agosto de 2017, Código 111577757629, Contrato 781 de 2017; Convocatoria Programática Ciencias de la Salud 2014-2015 CODI-UdeA, and Convocatoria N.727-2015 Doctorados Nacionales, Colciencias, 2015. The researchers had no financial conflicts to disclose.

Ancestry was a significant predictor of response to lithium by adults with bipolar disorder (BPD), based on data from 172 individuals.

Lithium remains the first-line treatment for BPD, but clinical improvement occurs in less than one-third of patients, and factors that might affect response, especially genetic factors, have not been well studied, wrote Ana M. Díaz-Zuluaga, MD, of University of Antioquia, Medellín, Colombia, and colleagues.

Previous genetic research identified four linked single nucleotide polymorphisms (SNPs) in a single locus on chromosome 21 that were associated with lithium response, but the study was limited to individuals with European and Asian ancestry, the researchers said.

In a study published in the Journal of Affective Disorders, the researchers identified 172 adults aged 18 and older with a diagnosis of BPD I or II based on the DSM-IV-TR criteria. Participants had been taking lithium continuously for at least 6 months. Lithium response was defined using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with BD, also known as the Alda scale. Total Alda scale scores of 7 or higher indicated a responder phenotype; scores less than 7 were considered nonresponders.

Ancestry was determined using DNA samples and the software Structure Version 2.2, and participants were classified as Amerindian, African, or European.

The overall response rate to lithium was 15.11% (26 of 172 patients). In a univariate analysis, no significant differences emerged between responders and nonresponders in demographics or clinical characteristics. However, patients responsive to lithium were significantly less likely of African ancestry, compared with nonresponders (0.1 vs. 0.2, P = .005) and more likely of European ancestry (0.5 vs. 0.3, P = .024), and had fewer depressive episodes (2 vs. 3.9, P = .002). The difference in responders vs. nonresponders of Amerindian ancestry was not statistically significant (0.4 vs. 0.5, P = .204).

The researchers then used machine learning based on Advanced Recursive Partitioning Approaches (ARPAs) to create classification trees with and without ancestry components for predicting response to lithium. “Variable importance analysis shows that the most important predictor is the probability of Amerindian ancestry component, followed by the Amerindian and European ancestral components individual variances, and then by the African and European ancestry components,” the researchers wrote.

Without the ancestry component, the sensitivity and specificity for predicting a treatment response to lithium were 50% and 94.5% respectively, with an area under the curve of 72.2%.

“However, when ancestral components are included in the model, the sensitivity and specificity are 93 % and 84 %, respectively,” with an AUC of 89.2%, the researchers said.

Clinical predictors of treatment response included disease duration, number of depressive episodes, total number of affective episodes, and number of manic episodes.

The findings were limited by several factors including the cross-sectional design and potential impact of other psychotropic drugs, the researchers noted. A replication of the study in an independent dataset is needed to validate the findings, they said.

However, the study is the first known to explore the effect of ancestry on bipolar patients’ response to lithium, and suggests that ancestry components have potential predictive value in the clinical setting that could support a more personalized approach to treatment, the researchers said.

The study was supported by PRISMA U.T., Colciencias, Invitación 990 del 3 de Agosto de 2017, Código 111577757629, Contrato 781 de 2017; Convocatoria Programática Ciencias de la Salud 2014-2015 CODI-UdeA, and Convocatoria N.727-2015 Doctorados Nacionales, Colciencias, 2015. The researchers had no financial conflicts to disclose.

The popular but expensive weight loss drug semaglutide (Wegovy, significantly reduced major adverse cardiovascular events (MACE) by 20% when given to patients, compared with those receiving placebo, in the pivotal SELECT trial, with more than 17,000 enrolled people with overweight or obesity and established cardiovascular disease (CVD), but no diabetes.

The finding should fuel improved patient access to this glucagon-like peptide-1 (GLP-1) agonist weight-loss agent that has historically been hindered by skepticism among U.S. payers, many of whom have criticized the health benefits and cost effectiveness of this drug in people whose only indication for treatment is overweight or obesity.

According to top-line results from SELECT released by Novo Nordisk on Aug. 8, the people randomly assigned to receive weekly 2.4-mg subcutaneous injections of semaglutide showed a significant 20% reduction in their incidence of the combined endpoint of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The announcement added that semaglutide treatment also significantly linked with a drop in the incidence of each of these individual three endpoints; the magnitude of these reductions, however, wasn’t specified, nor was the duration of treatment and follow-up.

The results also showed a level of safety and patient tolerance for weekly 2.4-mg injections of semaglutide that were consistent with prior reports on the agent. Semaglutide as Wegovy received marketing approval from the U.S. Food and Drug Administration in 2021 for weight loss, and in 2017 for glucose control in people with type 2 diabetes, at a weekly maximum dose of 2.0 mg (for which it’s marketed as Ozempic).

SELECT began in 2018 and randomly assigned 17,604 adults aged 45 years and older at more than 800 sites in 41 countries. The company’s announcement noted that the trial had accrued a total of 1,270 study participants with a first MACE event but did not break this total down based on treatment received.
 

‘A good result for patients’

“The topline results from SELECT are exciting, as preventing heart attacks and stroke with a drug that also lowers weight is very important for many patients, especially if the data also show – as I suspect they will – a meaningful improvement of quality of life for patients due to associated weight loss,” commented Naveed Sattar, PhD, a professor of metabolic medicine at the University of Glasgow who was not involved with the study.

Changing how obesity is regarded

“To date, there are no approved weight management medications proven to deliver effective weight management while also reducing the risk of heart attack, stroke, or cardiovascular death,” said Martin Holst Lange, executive vice president for development at Novo Nordisk, in the company’s press release.

“SELECT is a landmark trial and has demonstrated that semaglutide 2.4 mg has the potential to change how obesity is regarded and treated.”

Several of the early medical options for aiding weight loss had substantial adverse effects, including increased MACE rates, a history that led to pervasive wariness among physicians over the safety of antiobesity agents and the wisdom of using medically aided weight loss to produce health benefits.

This attitude also helped dampen health insurance coverage of weight-loss treatments. For example, Medicare has a long-standing policy against reimbursing the cost for medications that are used for the indication of weight loss, and a 2003 U.S. law prohibited part D plans from providing this coverage.

Semaglutide belongs to the class of agents that mimic the action of the incretin GLP-1. The introduction of this class of GLP-1 agonists for weight loss began in 2014 with the FDA’s approval of liraglutide (Saxenda), a daily subcutaneous injection that marked the first step toward establishing the class as safe and effective for weight loss and launching a new era in weight-loss treatment.

According to the Novo Nordisk announcement, a full report on results from SELECT will occur “at a scientific meeting later in 2023.”

SELECT is sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Sattar is a consultant to several companies that market GLP-1 receptor agonists, including Novo Nordisk and Lilly, but has had no involvement in SELECT.

A version of this article first appeared on Medscape.com.

The popular but expensive weight loss drug semaglutide (Wegovy, significantly reduced major adverse cardiovascular events (MACE) by 20% when given to patients, compared with those receiving placebo, in the pivotal SELECT trial, with more than 17,000 enrolled people with overweight or obesity and established cardiovascular disease (CVD), but no diabetes.

The finding should fuel improved patient access to this glucagon-like peptide-1 (GLP-1) agonist weight-loss agent that has historically been hindered by skepticism among U.S. payers, many of whom have criticized the health benefits and cost effectiveness of this drug in people whose only indication for treatment is overweight or obesity.

According to top-line results from SELECT released by Novo Nordisk on Aug. 8, the people randomly assigned to receive weekly 2.4-mg subcutaneous injections of semaglutide showed a significant 20% reduction in their incidence of the combined endpoint of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The announcement added that semaglutide treatment also significantly linked with a drop in the incidence of each of these individual three endpoints; the magnitude of these reductions, however, wasn’t specified, nor was the duration of treatment and follow-up.

The results also showed a level of safety and patient tolerance for weekly 2.4-mg injections of semaglutide that were consistent with prior reports on the agent. Semaglutide as Wegovy received marketing approval from the U.S. Food and Drug Administration in 2021 for weight loss, and in 2017 for glucose control in people with type 2 diabetes, at a weekly maximum dose of 2.0 mg (for which it’s marketed as Ozempic).

SELECT began in 2018 and randomly assigned 17,604 adults aged 45 years and older at more than 800 sites in 41 countries. The company’s announcement noted that the trial had accrued a total of 1,270 study participants with a first MACE event but did not break this total down based on treatment received.
 

‘A good result for patients’

“The topline results from SELECT are exciting, as preventing heart attacks and stroke with a drug that also lowers weight is very important for many patients, especially if the data also show – as I suspect they will – a meaningful improvement of quality of life for patients due to associated weight loss,” commented Naveed Sattar, PhD, a professor of metabolic medicine at the University of Glasgow who was not involved with the study.

Changing how obesity is regarded

“To date, there are no approved weight management medications proven to deliver effective weight management while also reducing the risk of heart attack, stroke, or cardiovascular death,” said Martin Holst Lange, executive vice president for development at Novo Nordisk, in the company’s press release.

“SELECT is a landmark trial and has demonstrated that semaglutide 2.4 mg has the potential to change how obesity is regarded and treated.”

Several of the early medical options for aiding weight loss had substantial adverse effects, including increased MACE rates, a history that led to pervasive wariness among physicians over the safety of antiobesity agents and the wisdom of using medically aided weight loss to produce health benefits.

This attitude also helped dampen health insurance coverage of weight-loss treatments. For example, Medicare has a long-standing policy against reimbursing the cost for medications that are used for the indication of weight loss, and a 2003 U.S. law prohibited part D plans from providing this coverage.

Semaglutide belongs to the class of agents that mimic the action of the incretin GLP-1. The introduction of this class of GLP-1 agonists for weight loss began in 2014 with the FDA’s approval of liraglutide (Saxenda), a daily subcutaneous injection that marked the first step toward establishing the class as safe and effective for weight loss and launching a new era in weight-loss treatment.

According to the Novo Nordisk announcement, a full report on results from SELECT will occur “at a scientific meeting later in 2023.”

SELECT is sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Sattar is a consultant to several companies that market GLP-1 receptor agonists, including Novo Nordisk and Lilly, but has had no involvement in SELECT.

A version of this article first appeared on Medscape.com.

The popular but expensive weight loss drug semaglutide (Wegovy, significantly reduced major adverse cardiovascular events (MACE) by 20% when given to patients, compared with those receiving placebo, in the pivotal SELECT trial, with more than 17,000 enrolled people with overweight or obesity and established cardiovascular disease (CVD), but no diabetes.

The finding should fuel improved patient access to this glucagon-like peptide-1 (GLP-1) agonist weight-loss agent that has historically been hindered by skepticism among U.S. payers, many of whom have criticized the health benefits and cost effectiveness of this drug in people whose only indication for treatment is overweight or obesity.

According to top-line results from SELECT released by Novo Nordisk on Aug. 8, the people randomly assigned to receive weekly 2.4-mg subcutaneous injections of semaglutide showed a significant 20% reduction in their incidence of the combined endpoint of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The announcement added that semaglutide treatment also significantly linked with a drop in the incidence of each of these individual three endpoints; the magnitude of these reductions, however, wasn’t specified, nor was the duration of treatment and follow-up.

The results also showed a level of safety and patient tolerance for weekly 2.4-mg injections of semaglutide that were consistent with prior reports on the agent. Semaglutide as Wegovy received marketing approval from the U.S. Food and Drug Administration in 2021 for weight loss, and in 2017 for glucose control in people with type 2 diabetes, at a weekly maximum dose of 2.0 mg (for which it’s marketed as Ozempic).

SELECT began in 2018 and randomly assigned 17,604 adults aged 45 years and older at more than 800 sites in 41 countries. The company’s announcement noted that the trial had accrued a total of 1,270 study participants with a first MACE event but did not break this total down based on treatment received.
 

‘A good result for patients’

“The topline results from SELECT are exciting, as preventing heart attacks and stroke with a drug that also lowers weight is very important for many patients, especially if the data also show – as I suspect they will – a meaningful improvement of quality of life for patients due to associated weight loss,” commented Naveed Sattar, PhD, a professor of metabolic medicine at the University of Glasgow who was not involved with the study.

Changing how obesity is regarded

“To date, there are no approved weight management medications proven to deliver effective weight management while also reducing the risk of heart attack, stroke, or cardiovascular death,” said Martin Holst Lange, executive vice president for development at Novo Nordisk, in the company’s press release.

“SELECT is a landmark trial and has demonstrated that semaglutide 2.4 mg has the potential to change how obesity is regarded and treated.”

Several of the early medical options for aiding weight loss had substantial adverse effects, including increased MACE rates, a history that led to pervasive wariness among physicians over the safety of antiobesity agents and the wisdom of using medically aided weight loss to produce health benefits.

This attitude also helped dampen health insurance coverage of weight-loss treatments. For example, Medicare has a long-standing policy against reimbursing the cost for medications that are used for the indication of weight loss, and a 2003 U.S. law prohibited part D plans from providing this coverage.

Semaglutide belongs to the class of agents that mimic the action of the incretin GLP-1. The introduction of this class of GLP-1 agonists for weight loss began in 2014 with the FDA’s approval of liraglutide (Saxenda), a daily subcutaneous injection that marked the first step toward establishing the class as safe and effective for weight loss and launching a new era in weight-loss treatment.

According to the Novo Nordisk announcement, a full report on results from SELECT will occur “at a scientific meeting later in 2023.”

SELECT is sponsored by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Sattar is a consultant to several companies that market GLP-1 receptor agonists, including Novo Nordisk and Lilly, but has had no involvement in SELECT.

A version of this article first appeared on Medscape.com.

Zolpidem (Ambien) is a well-known sedative for sleep. Letairis (Ambrisentan) is a vasodilator for the treatment of pulmonary arterial hypertension. Citalopram (Celexa) is an antidepressant; escitalopram (Lexapro) is prescribed for anxiety and depression.
 

Those are just 4 of the more than 80 pairs of drug names that the Institute for Safe Medication Practices recently added to its list of confusing drug names. The aim is to increase awareness about the potential for a serious medication mistake when the wrong drug is given because of drug names that look and sound similar.

Awareness of these drug names, however, is just the first step in preventing medication mistakes. Health care providers should take a number of other steps as well, experts said.

ISMP launched its confusing drug names list, previously called look-alike, sound-alike (LASA) drugs, in 2008. The new list is an update of the 2019 version, said Michael J. Gaunt, PharmD, senior manager of error reporting programs for the ISMP, which focuses on the prevention of medication mistakes. The new entries were chosen on the basis of a number of factors, including ISMP’s analysis of recent medication mishap reports that were submitted to it.

The ISMP list now includes about 528 drug pairs, Dr. Gaunt said. The list is long, he said, partly because each pair is listed twice, so readers can cross reference. For instance, hydralazine and hydroxyzine are listed in one entry in the list, and hydroxyzine and hydralazine are listed in another.

Brand Institute in Miami has named, among other drugs, Entresto, Rybelsus, and Lunesta. The regulatory arm of the company, the Drug Safety Institute, “considers drug names that have been confused as an important part of our comprehensive drug name assessments,” Todd Bridges, global president of the institute, said in an emailed statement. Information on the confusing drug names are incorporated into the company’s proprietary algorithm and is used when developing brand names for drugs. “We continually update this algorithm as new drug names that are often confused are identified,” Mr. Bridges said.
 

Confusing drug names: Ongoing issue

The length of the list, as well as the latest additions, are not surprising, said Mary Ann Kliethermes, PharmD, director of medication safety and quality for the American Society of Health-System Pharmacists, a membership organization of about 60,000 pharmacists who practice in inpatient and outpatient settings.

“I’ve been in practice over 45 years,” she said, “and this has been a problem ever since I have been in practice.” The sheer volume of new drugs is one reason, she said. From 2013 through 2022, the U.S. Food and Drug Administration approved an average of 43 novel drugs per year, according to a report from its Center for Drug Evaluation and Research. “Since the 90s, this [confusion about similar drug names] has happened,” Dr. Kliethermes said.

According to a 2023 report, about 7,000-9,000 people die each year in the United States as the result of a medication error. However, it’s impossible to say for sure what percentage of those errors involve name confusion, Dr. Gaunt said.

Not all the mistakes are reported. Some that are reported are dramatic and deadly. In 2022, a Tennessee nurse was convicted of gross neglect and negligent homicide. She was sentenced to 3 years’ probation after she mistakenly gave vercuronium, an anesthetic agent, instead of the sedative Versed to a patient, and the woman died.
 

Updated list: A closer look

Many of the new drug pairs that are listed in the update are cephalosporins, said Dr. Kliethermes, who reviewed the new list for this news organization. In all, 20 of the latest 82 additions are cephalosporins. These include drugs such as cefazolin, which can be confused with cefotetan, and vice versa. These drugs have been around since the 1980s, she said, but “they needed to be on there.” Even in the 1980s, it was becoming difficult to differentiate them, and there were fewer drugs in that class then, she said.

Influenza vaccines made the new list, too. Fluzone High-Dose Quadrivalent can be confused with fluzone quadrivalent. Other new additions: hydrochlorothiazide and hydroxychloroquine, Lasik and Wakix, Pitressin and Pitocin, Remeron and Rozerem.
 

Beyond the list

While it’s not possible to pinpoint how big a problem name confusion is in causing medication mistakes, “it is certainly still an issue,” Dr. Gaunt said. A variety of practices can reduce that risk substantially, Dr. Gaunt and Dr. Kliethermes agreed.

Tall-man lettering. Both the FDA and the ISMP recommend the use of so-called tall-man lettering (TML), which involves the use of uppercase letters, sometimes in boldface, to distinguish similar names on product labels and elsewhere. Examples include vinBLAStine and vinCRIStine.

Electronic prescribing. “It eliminates the risk of handwriting confusion,” Dr. Gaunt said. However, electronic prescribing can have a downside, Dr. Kliethermes said. When ordering medication, a person may type in a few letters and may then be presented with a prompt that lists several drug names, and it can be easy to click the wrong one. For that reason, ISMP and other experts recommend typing at least five letters when searching for a medication in an electronic system.

Use both brand and generic names on labels and prescriptions.

Write the indication. That can serve as a double check. If a prescription for Ambien says “For sleep,” there’s probably less risk of filling a prescription for ambrisentan, the vasodilator.

Smart formulary additions. When hospitals add medications to their formularies, “part of that formulary assessment should include looking at the potential risk for errors,” Dr. Gaunt said. This involves keeping an eye out for confusing names and similar packaging. “Do that analysis up front and put in strategies to minimize that. Maybe you look for a different drug [for the same use] that has a different name.” Or choose a different manufacturer, so the medication would at least have a different container.

Use bar code scanning. Suppose a pharmacist goes to the shelf and pulls the wrong drug. “Bar code scanning provides the opportunity to catch the error,” Dr. Gaunt said. Many community pharmacies now have bar code scanning. ISMP just issued best practices for community pharmacies, Dr. Gaunt said, and these include the use of bar code scanning and other measures.

Educate consumers. Health care providers can educate consumers on how to minimize the risk of getting the wrong drug, Dr. Gaunt said. When patients are picking up a prescription, suggest they look at the container label; if it looks different from previous prescriptions of the same medicine, ask the pharmacist for an explanation. Some patients just pass it off, Dr. Gaunt said, figuring the pharmacist or health plan switched manufacturers of their medication.

Access the list. The entire list is on the ISMP site and is accessible after free registration.
 

Goal: Preventing confusion

The FDA has provided guidance for industry on naming drugs not yet approved so that the proposed names are not too similar in sound or appearance to those already on the market. Included in the lengthy document are checklists, such as, “Across a range of dialects, are the names consistently pronounced differently?” and “Are the lengths of the names dissimilar when scripted?” (Lengths are considered different if they differ by two or more letters.)

The FDA also offers the phonetic and orthographic computer analysis (POCA) program, a software tool that employs an advanced algorithm to evaluate similarities between two drug names. The data sources are updated regularly as new drugs are approved.
 

Liability update

The problem may be decreasing. In a 2020 report, researchers used pharmacists’ professional liability claim data from the Healthcare Providers Service Organization. They compared 2018 data on claims with 2013 data. The percentage of claims associated with wrong drug dispensing errors declined from 43.8% in 2013 to 36.8% in 2018. Wrong dose claims also declined, from 31.5% to 15.3%.

These researchers concluded that technology and automation have contributed to the prevention of medication errors caused by the use of the wrong drug and the wrong dose, but mistakes continue, owing to system and human errors.

A version of this article first appeared on Medscape.com.

Zolpidem (Ambien) is a well-known sedative for sleep. Letairis (Ambrisentan) is a vasodilator for the treatment of pulmonary arterial hypertension. Citalopram (Celexa) is an antidepressant; escitalopram (Lexapro) is prescribed for anxiety and depression.
 

Those are just 4 of the more than 80 pairs of drug names that the Institute for Safe Medication Practices recently added to its list of confusing drug names. The aim is to increase awareness about the potential for a serious medication mistake when the wrong drug is given because of drug names that look and sound similar.

Awareness of these drug names, however, is just the first step in preventing medication mistakes. Health care providers should take a number of other steps as well, experts said.

ISMP launched its confusing drug names list, previously called look-alike, sound-alike (LASA) drugs, in 2008. The new list is an update of the 2019 version, said Michael J. Gaunt, PharmD, senior manager of error reporting programs for the ISMP, which focuses on the prevention of medication mistakes. The new entries were chosen on the basis of a number of factors, including ISMP’s analysis of recent medication mishap reports that were submitted to it.

The ISMP list now includes about 528 drug pairs, Dr. Gaunt said. The list is long, he said, partly because each pair is listed twice, so readers can cross reference. For instance, hydralazine and hydroxyzine are listed in one entry in the list, and hydroxyzine and hydralazine are listed in another.

Brand Institute in Miami has named, among other drugs, Entresto, Rybelsus, and Lunesta. The regulatory arm of the company, the Drug Safety Institute, “considers drug names that have been confused as an important part of our comprehensive drug name assessments,” Todd Bridges, global president of the institute, said in an emailed statement. Information on the confusing drug names are incorporated into the company’s proprietary algorithm and is used when developing brand names for drugs. “We continually update this algorithm as new drug names that are often confused are identified,” Mr. Bridges said.
 

Confusing drug names: Ongoing issue

The length of the list, as well as the latest additions, are not surprising, said Mary Ann Kliethermes, PharmD, director of medication safety and quality for the American Society of Health-System Pharmacists, a membership organization of about 60,000 pharmacists who practice in inpatient and outpatient settings.

“I’ve been in practice over 45 years,” she said, “and this has been a problem ever since I have been in practice.” The sheer volume of new drugs is one reason, she said. From 2013 through 2022, the U.S. Food and Drug Administration approved an average of 43 novel drugs per year, according to a report from its Center for Drug Evaluation and Research. “Since the 90s, this [confusion about similar drug names] has happened,” Dr. Kliethermes said.

According to a 2023 report, about 7,000-9,000 people die each year in the United States as the result of a medication error. However, it’s impossible to say for sure what percentage of those errors involve name confusion, Dr. Gaunt said.

Not all the mistakes are reported. Some that are reported are dramatic and deadly. In 2022, a Tennessee nurse was convicted of gross neglect and negligent homicide. She was sentenced to 3 years’ probation after she mistakenly gave vercuronium, an anesthetic agent, instead of the sedative Versed to a patient, and the woman died.
 

Updated list: A closer look

Many of the new drug pairs that are listed in the update are cephalosporins, said Dr. Kliethermes, who reviewed the new list for this news organization. In all, 20 of the latest 82 additions are cephalosporins. These include drugs such as cefazolin, which can be confused with cefotetan, and vice versa. These drugs have been around since the 1980s, she said, but “they needed to be on there.” Even in the 1980s, it was becoming difficult to differentiate them, and there were fewer drugs in that class then, she said.

Influenza vaccines made the new list, too. Fluzone High-Dose Quadrivalent can be confused with fluzone quadrivalent. Other new additions: hydrochlorothiazide and hydroxychloroquine, Lasik and Wakix, Pitressin and Pitocin, Remeron and Rozerem.
 

Beyond the list

While it’s not possible to pinpoint how big a problem name confusion is in causing medication mistakes, “it is certainly still an issue,” Dr. Gaunt said. A variety of practices can reduce that risk substantially, Dr. Gaunt and Dr. Kliethermes agreed.

Tall-man lettering. Both the FDA and the ISMP recommend the use of so-called tall-man lettering (TML), which involves the use of uppercase letters, sometimes in boldface, to distinguish similar names on product labels and elsewhere. Examples include vinBLAStine and vinCRIStine.

Electronic prescribing. “It eliminates the risk of handwriting confusion,” Dr. Gaunt said. However, electronic prescribing can have a downside, Dr. Kliethermes said. When ordering medication, a person may type in a few letters and may then be presented with a prompt that lists several drug names, and it can be easy to click the wrong one. For that reason, ISMP and other experts recommend typing at least five letters when searching for a medication in an electronic system.

Use both brand and generic names on labels and prescriptions.

Write the indication. That can serve as a double check. If a prescription for Ambien says “For sleep,” there’s probably less risk of filling a prescription for ambrisentan, the vasodilator.

Smart formulary additions. When hospitals add medications to their formularies, “part of that formulary assessment should include looking at the potential risk for errors,” Dr. Gaunt said. This involves keeping an eye out for confusing names and similar packaging. “Do that analysis up front and put in strategies to minimize that. Maybe you look for a different drug [for the same use] that has a different name.” Or choose a different manufacturer, so the medication would at least have a different container.

Use bar code scanning. Suppose a pharmacist goes to the shelf and pulls the wrong drug. “Bar code scanning provides the opportunity to catch the error,” Dr. Gaunt said. Many community pharmacies now have bar code scanning. ISMP just issued best practices for community pharmacies, Dr. Gaunt said, and these include the use of bar code scanning and other measures.

Educate consumers. Health care providers can educate consumers on how to minimize the risk of getting the wrong drug, Dr. Gaunt said. When patients are picking up a prescription, suggest they look at the container label; if it looks different from previous prescriptions of the same medicine, ask the pharmacist for an explanation. Some patients just pass it off, Dr. Gaunt said, figuring the pharmacist or health plan switched manufacturers of their medication.

Access the list. The entire list is on the ISMP site and is accessible after free registration.
 

Goal: Preventing confusion

The FDA has provided guidance for industry on naming drugs not yet approved so that the proposed names are not too similar in sound or appearance to those already on the market. Included in the lengthy document are checklists, such as, “Across a range of dialects, are the names consistently pronounced differently?” and “Are the lengths of the names dissimilar when scripted?” (Lengths are considered different if they differ by two or more letters.)

The FDA also offers the phonetic and orthographic computer analysis (POCA) program, a software tool that employs an advanced algorithm to evaluate similarities between two drug names. The data sources are updated regularly as new drugs are approved.
 

Liability update

The problem may be decreasing. In a 2020 report, researchers used pharmacists’ professional liability claim data from the Healthcare Providers Service Organization. They compared 2018 data on claims with 2013 data. The percentage of claims associated with wrong drug dispensing errors declined from 43.8% in 2013 to 36.8% in 2018. Wrong dose claims also declined, from 31.5% to 15.3%.

These researchers concluded that technology and automation have contributed to the prevention of medication errors caused by the use of the wrong drug and the wrong dose, but mistakes continue, owing to system and human errors.

A version of this article first appeared on Medscape.com.

Zolpidem (Ambien) is a well-known sedative for sleep. Letairis (Ambrisentan) is a vasodilator for the treatment of pulmonary arterial hypertension. Citalopram (Celexa) is an antidepressant; escitalopram (Lexapro) is prescribed for anxiety and depression.
 

Those are just 4 of the more than 80 pairs of drug names that the Institute for Safe Medication Practices recently added to its list of confusing drug names. The aim is to increase awareness about the potential for a serious medication mistake when the wrong drug is given because of drug names that look and sound similar.

Awareness of these drug names, however, is just the first step in preventing medication mistakes. Health care providers should take a number of other steps as well, experts said.

ISMP launched its confusing drug names list, previously called look-alike, sound-alike (LASA) drugs, in 2008. The new list is an update of the 2019 version, said Michael J. Gaunt, PharmD, senior manager of error reporting programs for the ISMP, which focuses on the prevention of medication mistakes. The new entries were chosen on the basis of a number of factors, including ISMP’s analysis of recent medication mishap reports that were submitted to it.

The ISMP list now includes about 528 drug pairs, Dr. Gaunt said. The list is long, he said, partly because each pair is listed twice, so readers can cross reference. For instance, hydralazine and hydroxyzine are listed in one entry in the list, and hydroxyzine and hydralazine are listed in another.

Brand Institute in Miami has named, among other drugs, Entresto, Rybelsus, and Lunesta. The regulatory arm of the company, the Drug Safety Institute, “considers drug names that have been confused as an important part of our comprehensive drug name assessments,” Todd Bridges, global president of the institute, said in an emailed statement. Information on the confusing drug names are incorporated into the company’s proprietary algorithm and is used when developing brand names for drugs. “We continually update this algorithm as new drug names that are often confused are identified,” Mr. Bridges said.
 

Confusing drug names: Ongoing issue

The length of the list, as well as the latest additions, are not surprising, said Mary Ann Kliethermes, PharmD, director of medication safety and quality for the American Society of Health-System Pharmacists, a membership organization of about 60,000 pharmacists who practice in inpatient and outpatient settings.

“I’ve been in practice over 45 years,” she said, “and this has been a problem ever since I have been in practice.” The sheer volume of new drugs is one reason, she said. From 2013 through 2022, the U.S. Food and Drug Administration approved an average of 43 novel drugs per year, according to a report from its Center for Drug Evaluation and Research. “Since the 90s, this [confusion about similar drug names] has happened,” Dr. Kliethermes said.

According to a 2023 report, about 7,000-9,000 people die each year in the United States as the result of a medication error. However, it’s impossible to say for sure what percentage of those errors involve name confusion, Dr. Gaunt said.

Not all the mistakes are reported. Some that are reported are dramatic and deadly. In 2022, a Tennessee nurse was convicted of gross neglect and negligent homicide. She was sentenced to 3 years’ probation after she mistakenly gave vercuronium, an anesthetic agent, instead of the sedative Versed to a patient, and the woman died.
 

Updated list: A closer look

Many of the new drug pairs that are listed in the update are cephalosporins, said Dr. Kliethermes, who reviewed the new list for this news organization. In all, 20 of the latest 82 additions are cephalosporins. These include drugs such as cefazolin, which can be confused with cefotetan, and vice versa. These drugs have been around since the 1980s, she said, but “they needed to be on there.” Even in the 1980s, it was becoming difficult to differentiate them, and there were fewer drugs in that class then, she said.

Influenza vaccines made the new list, too. Fluzone High-Dose Quadrivalent can be confused with fluzone quadrivalent. Other new additions: hydrochlorothiazide and hydroxychloroquine, Lasik and Wakix, Pitressin and Pitocin, Remeron and Rozerem.
 

Beyond the list

While it’s not possible to pinpoint how big a problem name confusion is in causing medication mistakes, “it is certainly still an issue,” Dr. Gaunt said. A variety of practices can reduce that risk substantially, Dr. Gaunt and Dr. Kliethermes agreed.

Tall-man lettering. Both the FDA and the ISMP recommend the use of so-called tall-man lettering (TML), which involves the use of uppercase letters, sometimes in boldface, to distinguish similar names on product labels and elsewhere. Examples include vinBLAStine and vinCRIStine.

Electronic prescribing. “It eliminates the risk of handwriting confusion,” Dr. Gaunt said. However, electronic prescribing can have a downside, Dr. Kliethermes said. When ordering medication, a person may type in a few letters and may then be presented with a prompt that lists several drug names, and it can be easy to click the wrong one. For that reason, ISMP and other experts recommend typing at least five letters when searching for a medication in an electronic system.

Use both brand and generic names on labels and prescriptions.

Write the indication. That can serve as a double check. If a prescription for Ambien says “For sleep,” there’s probably less risk of filling a prescription for ambrisentan, the vasodilator.

Smart formulary additions. When hospitals add medications to their formularies, “part of that formulary assessment should include looking at the potential risk for errors,” Dr. Gaunt said. This involves keeping an eye out for confusing names and similar packaging. “Do that analysis up front and put in strategies to minimize that. Maybe you look for a different drug [for the same use] that has a different name.” Or choose a different manufacturer, so the medication would at least have a different container.

Use bar code scanning. Suppose a pharmacist goes to the shelf and pulls the wrong drug. “Bar code scanning provides the opportunity to catch the error,” Dr. Gaunt said. Many community pharmacies now have bar code scanning. ISMP just issued best practices for community pharmacies, Dr. Gaunt said, and these include the use of bar code scanning and other measures.

Educate consumers. Health care providers can educate consumers on how to minimize the risk of getting the wrong drug, Dr. Gaunt said. When patients are picking up a prescription, suggest they look at the container label; if it looks different from previous prescriptions of the same medicine, ask the pharmacist for an explanation. Some patients just pass it off, Dr. Gaunt said, figuring the pharmacist or health plan switched manufacturers of their medication.

Access the list. The entire list is on the ISMP site and is accessible after free registration.
 

Goal: Preventing confusion

The FDA has provided guidance for industry on naming drugs not yet approved so that the proposed names are not too similar in sound or appearance to those already on the market. Included in the lengthy document are checklists, such as, “Across a range of dialects, are the names consistently pronounced differently?” and “Are the lengths of the names dissimilar when scripted?” (Lengths are considered different if they differ by two or more letters.)

The FDA also offers the phonetic and orthographic computer analysis (POCA) program, a software tool that employs an advanced algorithm to evaluate similarities between two drug names. The data sources are updated regularly as new drugs are approved.
 

Liability update

The problem may be decreasing. In a 2020 report, researchers used pharmacists’ professional liability claim data from the Healthcare Providers Service Organization. They compared 2018 data on claims with 2013 data. The percentage of claims associated with wrong drug dispensing errors declined from 43.8% in 2013 to 36.8% in 2018. Wrong dose claims also declined, from 31.5% to 15.3%.

These researchers concluded that technology and automation have contributed to the prevention of medication errors caused by the use of the wrong drug and the wrong dose, but mistakes continue, owing to system and human errors.

A version of this article first appeared on Medscape.com.

TOPLINE:
 

Taking a proton pump inhibitor (PPI) with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib could diminish the full therapeutic benefit of palbociclib in women with breast cancer and lead to worse progression-free survival (PFS) and overall survival, new data suggest.

METHODOLOGY:

• The study retrospectively identified 1,310 women with advanced breast cancer receiving palbociclib using South Korean nationwide claims data.
• Overall, 344 women in the concomitant group, those who were coadministered a PPI for more than one-third of their palbociclib treatment duration, were propensity-score matched to 966 women who did not have PPI exposure: the nonconcomitant group.
• Main outcomes were time to progression and death, presented as PFS and overall survival.

TAKEAWAY:

• Median clinical PFS was significantly shorter by about 15 months in the concomitant PPI group vs. the nonconcomitant group (25.3 vs. 39.8 months; adjusted hazard ratio, 1.76).
• Concomitant PPI use was also associated with shorter overall survival (HR, 2.71).
• Overall, 83.1% of patients in the concomitant group were alive at 1 year vs. 94.0% in the nonconcomitant group (P < .001), and 69.5% vs. 89.3%, respectively, were alive at 2 years (P < .001), though the median overall survival was not reached in either group.
• In a subgroup analysis, concomitant PPI use was associated with shorter clinical PFS (HR, 1.75 for those receiving endocrine-sensitive treatment and 1.82 for those receiving endocrine-resistant treatment), and shorter overall survival (HR, 2.68 in the endocrine-sensitive subgroup and 2.98 in the endocrine-resistant subgroup).

IN PRACTICE:

“The findings suggest that taking PPIs with palbociclib may interrupt the full therapeutic benefits of palbociclib,” the authors conclude. “Physicians should be cautious when prescribing PPIs to patients who are receiving palbociclib.”

SOURCE:

The study, led by Ju-Eun Lee, MS, PharmD, School of Pharmacy, Sungkyunkwan University, South Korea, was published online in JAMA Network Open.

LIMITATIONS:

The study was limited by its retrospective design and use of claims data as well as the inability to confirm whether patients actually took the PPI medication.

DISCLOSURES:

The authors report no relevant financial relationships. The study reported no commercial funding.

A version of this article first appeared on Medscape.com.

TOPLINE:
 

Taking a proton pump inhibitor (PPI) with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib could diminish the full therapeutic benefit of palbociclib in women with breast cancer and lead to worse progression-free survival (PFS) and overall survival, new data suggest.

METHODOLOGY:

• The study retrospectively identified 1,310 women with advanced breast cancer receiving palbociclib using South Korean nationwide claims data.
• Overall, 344 women in the concomitant group, those who were coadministered a PPI for more than one-third of their palbociclib treatment duration, were propensity-score matched to 966 women who did not have PPI exposure: the nonconcomitant group.
• Main outcomes were time to progression and death, presented as PFS and overall survival.

TAKEAWAY:

• Median clinical PFS was significantly shorter by about 15 months in the concomitant PPI group vs. the nonconcomitant group (25.3 vs. 39.8 months; adjusted hazard ratio, 1.76).
• Concomitant PPI use was also associated with shorter overall survival (HR, 2.71).
• Overall, 83.1% of patients in the concomitant group were alive at 1 year vs. 94.0% in the nonconcomitant group (P < .001), and 69.5% vs. 89.3%, respectively, were alive at 2 years (P < .001), though the median overall survival was not reached in either group.
• In a subgroup analysis, concomitant PPI use was associated with shorter clinical PFS (HR, 1.75 for those receiving endocrine-sensitive treatment and 1.82 for those receiving endocrine-resistant treatment), and shorter overall survival (HR, 2.68 in the endocrine-sensitive subgroup and 2.98 in the endocrine-resistant subgroup).

IN PRACTICE:

“The findings suggest that taking PPIs with palbociclib may interrupt the full therapeutic benefits of palbociclib,” the authors conclude. “Physicians should be cautious when prescribing PPIs to patients who are receiving palbociclib.”

SOURCE:

The study, led by Ju-Eun Lee, MS, PharmD, School of Pharmacy, Sungkyunkwan University, South Korea, was published online in JAMA Network Open.

LIMITATIONS:

The study was limited by its retrospective design and use of claims data as well as the inability to confirm whether patients actually took the PPI medication.

DISCLOSURES:

The authors report no relevant financial relationships. The study reported no commercial funding.

A version of this article first appeared on Medscape.com.

TOPLINE:
 

Taking a proton pump inhibitor (PPI) with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib could diminish the full therapeutic benefit of palbociclib in women with breast cancer and lead to worse progression-free survival (PFS) and overall survival, new data suggest.

METHODOLOGY:

• The study retrospectively identified 1,310 women with advanced breast cancer receiving palbociclib using South Korean nationwide claims data.
• Overall, 344 women in the concomitant group, those who were coadministered a PPI for more than one-third of their palbociclib treatment duration, were propensity-score matched to 966 women who did not have PPI exposure: the nonconcomitant group.
• Main outcomes were time to progression and death, presented as PFS and overall survival.

TAKEAWAY:

• Median clinical PFS was significantly shorter by about 15 months in the concomitant PPI group vs. the nonconcomitant group (25.3 vs. 39.8 months; adjusted hazard ratio, 1.76).
• Concomitant PPI use was also associated with shorter overall survival (HR, 2.71).
• Overall, 83.1% of patients in the concomitant group were alive at 1 year vs. 94.0% in the nonconcomitant group (P < .001), and 69.5% vs. 89.3%, respectively, were alive at 2 years (P < .001), though the median overall survival was not reached in either group.
• In a subgroup analysis, concomitant PPI use was associated with shorter clinical PFS (HR, 1.75 for those receiving endocrine-sensitive treatment and 1.82 for those receiving endocrine-resistant treatment), and shorter overall survival (HR, 2.68 in the endocrine-sensitive subgroup and 2.98 in the endocrine-resistant subgroup).

IN PRACTICE:

“The findings suggest that taking PPIs with palbociclib may interrupt the full therapeutic benefits of palbociclib,” the authors conclude. “Physicians should be cautious when prescribing PPIs to patients who are receiving palbociclib.”

SOURCE:

The study, led by Ju-Eun Lee, MS, PharmD, School of Pharmacy, Sungkyunkwan University, South Korea, was published online in JAMA Network Open.

LIMITATIONS:

The study was limited by its retrospective design and use of claims data as well as the inability to confirm whether patients actually took the PPI medication.

DISCLOSURES:

The authors report no relevant financial relationships. The study reported no commercial funding.

A version of this article first appeared on Medscape.com.

A daily prednisolone dose of 5 mg or higher is associated with increased risk for major adverse cardiovascular events (MACE) among patients with rheumatoid arthritis (RA), data suggest. Patients taking daily doses below this threshold did not appear to have an increased risk of MACE, compared with those not taking glucocorticoids (GCs).

Chinese University of Hong Kong

Is there a ‘safe’ dose for glucocorticoids?

To analyze this relationship, Dr. Lam and colleagues used the Hospital Authority Data Collaboration Laboratory, a citywide health care database. The investigators recruited patients with RA who had no history of MACE from 2006 to 2015 and followed them until the end of 2018. The primary outcome was the first occurrence of a MACE, defined as a composite of myocardial infarction (MI), unstable angina, ischemic or hemorrhagic cerebrovascular accident, transient ischemic attack, and CV death.

The study was published in Annals of the Rheumatic Diseases.

The analysis included 12,233 patients with RA and had over 105,826 person-years of follow-up. The average follow-up time was 8.7 years. During the study period, 860 patients had their first MACE. After controlling for confounding factors, a daily prednisolone dose of 5 mg or higher doubled the risk for MACE, compared with GC nonusers. MACE risk increased by 7% per month.

University of Wisconsin School of Medicine and Public Health

Long-term glucocorticoid use discouraged

Daily doses of less than 5 mg were not associated with higher MACE risk, but more research is necessary to understand whether these low doses are clinically efficacious, Dr. Tam said. “The study results suggest that a very-low-dose GC (less than 5 mg prednisolone daily) may be cardiovascular risk–neutral. However, further evaluation is needed to determine whether this dose is therapeutic. Other potential side effects, such as bone loss, increased infection risk, dyslipidemia, and hyperglycemia, should also be considered.”

Both the American College of Rheumatology and the European Alliance of Associations for Rheumatology acknowledge that short-term GCs may be necessary for some RA patients, but they emphasize using the smallest necessary dose for the shortest period possible because of the known toxicity of GCs.

“We recommend stopping GCs as soon as it is clinically feasible, in line with previous recommendations, until these issues are investigated further,” Dr. Tam added.

Dr. Bartels agreed that long-term use of GCs should be avoided if possible, even at lower doses, because although CV risk may be less of an issue, studies have shown an increased risk for infection even at GC doses of less than 5 mg a day.
 

How might risk increase with dose?

While the study showed a distinct difference in risk with doses of prednisolone higher and lower than 5 mg, more information on how risk increases with dose could be useful, said Beth Wallace, MD, an assistant professor in internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center. She was also unaffiliated with the research. “If someone is on 5-10 mg ... how much better is that than being on 10-20 mg or being on 20-30 mg?” she asked. While these study findings are “very important,” she said, it would be useful to know the risk associated with 7.5 mg vs. a higher dose.

University of Michigan

A version of this article first appeared on Medscape.com.

A daily prednisolone dose of 5 mg or higher is associated with increased risk for major adverse cardiovascular events (MACE) among patients with rheumatoid arthritis (RA), data suggest. Patients taking daily doses below this threshold did not appear to have an increased risk of MACE, compared with those not taking glucocorticoids (GCs).

Chinese University of Hong Kong

Is there a ‘safe’ dose for glucocorticoids?

To analyze this relationship, Dr. Lam and colleagues used the Hospital Authority Data Collaboration Laboratory, a citywide health care database. The investigators recruited patients with RA who had no history of MACE from 2006 to 2015 and followed them until the end of 2018. The primary outcome was the first occurrence of a MACE, defined as a composite of myocardial infarction (MI), unstable angina, ischemic or hemorrhagic cerebrovascular accident, transient ischemic attack, and CV death.

The study was published in Annals of the Rheumatic Diseases.

The analysis included 12,233 patients with RA and had over 105,826 person-years of follow-up. The average follow-up time was 8.7 years. During the study period, 860 patients had their first MACE. After controlling for confounding factors, a daily prednisolone dose of 5 mg or higher doubled the risk for MACE, compared with GC nonusers. MACE risk increased by 7% per month.

University of Wisconsin School of Medicine and Public Health

Long-term glucocorticoid use discouraged

Daily doses of less than 5 mg were not associated with higher MACE risk, but more research is necessary to understand whether these low doses are clinically efficacious, Dr. Tam said. “The study results suggest that a very-low-dose GC (less than 5 mg prednisolone daily) may be cardiovascular risk–neutral. However, further evaluation is needed to determine whether this dose is therapeutic. Other potential side effects, such as bone loss, increased infection risk, dyslipidemia, and hyperglycemia, should also be considered.”

Both the American College of Rheumatology and the European Alliance of Associations for Rheumatology acknowledge that short-term GCs may be necessary for some RA patients, but they emphasize using the smallest necessary dose for the shortest period possible because of the known toxicity of GCs.

“We recommend stopping GCs as soon as it is clinically feasible, in line with previous recommendations, until these issues are investigated further,” Dr. Tam added.

Dr. Bartels agreed that long-term use of GCs should be avoided if possible, even at lower doses, because although CV risk may be less of an issue, studies have shown an increased risk for infection even at GC doses of less than 5 mg a day.
 

How might risk increase with dose?

While the study showed a distinct difference in risk with doses of prednisolone higher and lower than 5 mg, more information on how risk increases with dose could be useful, said Beth Wallace, MD, an assistant professor in internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center. She was also unaffiliated with the research. “If someone is on 5-10 mg ... how much better is that than being on 10-20 mg or being on 20-30 mg?” she asked. While these study findings are “very important,” she said, it would be useful to know the risk associated with 7.5 mg vs. a higher dose.

University of Michigan

A version of this article first appeared on Medscape.com.

A daily prednisolone dose of 5 mg or higher is associated with increased risk for major adverse cardiovascular events (MACE) among patients with rheumatoid arthritis (RA), data suggest. Patients taking daily doses below this threshold did not appear to have an increased risk of MACE, compared with those not taking glucocorticoids (GCs).

Chinese University of Hong Kong

Is there a ‘safe’ dose for glucocorticoids?

To analyze this relationship, Dr. Lam and colleagues used the Hospital Authority Data Collaboration Laboratory, a citywide health care database. The investigators recruited patients with RA who had no history of MACE from 2006 to 2015 and followed them until the end of 2018. The primary outcome was the first occurrence of a MACE, defined as a composite of myocardial infarction (MI), unstable angina, ischemic or hemorrhagic cerebrovascular accident, transient ischemic attack, and CV death.

The study was published in Annals of the Rheumatic Diseases.

The analysis included 12,233 patients with RA and had over 105,826 person-years of follow-up. The average follow-up time was 8.7 years. During the study period, 860 patients had their first MACE. After controlling for confounding factors, a daily prednisolone dose of 5 mg or higher doubled the risk for MACE, compared with GC nonusers. MACE risk increased by 7% per month.

University of Wisconsin School of Medicine and Public Health

Long-term glucocorticoid use discouraged

Daily doses of less than 5 mg were not associated with higher MACE risk, but more research is necessary to understand whether these low doses are clinically efficacious, Dr. Tam said. “The study results suggest that a very-low-dose GC (less than 5 mg prednisolone daily) may be cardiovascular risk–neutral. However, further evaluation is needed to determine whether this dose is therapeutic. Other potential side effects, such as bone loss, increased infection risk, dyslipidemia, and hyperglycemia, should also be considered.”

Both the American College of Rheumatology and the European Alliance of Associations for Rheumatology acknowledge that short-term GCs may be necessary for some RA patients, but they emphasize using the smallest necessary dose for the shortest period possible because of the known toxicity of GCs.

“We recommend stopping GCs as soon as it is clinically feasible, in line with previous recommendations, until these issues are investigated further,” Dr. Tam added.

Dr. Bartels agreed that long-term use of GCs should be avoided if possible, even at lower doses, because although CV risk may be less of an issue, studies have shown an increased risk for infection even at GC doses of less than 5 mg a day.
 

How might risk increase with dose?

While the study showed a distinct difference in risk with doses of prednisolone higher and lower than 5 mg, more information on how risk increases with dose could be useful, said Beth Wallace, MD, an assistant professor in internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center. She was also unaffiliated with the research. “If someone is on 5-10 mg ... how much better is that than being on 10-20 mg or being on 20-30 mg?” she asked. While these study findings are “very important,” she said, it would be useful to know the risk associated with 7.5 mg vs. a higher dose.

University of Michigan

A version of this article first appeared on Medscape.com.

Use of dural-puncture epidural (DPE) shortened the onset time to surgical anesthesia by approximately 3 minutes, compared with standard epidural in patients undergoing cesarean delivery, based on data from 140 individuals.

DPE, while not new, has become more popular as an option for initiating labor analgesia, but data comparing DPE with standard epidural in conversion to surgical anesthesia for cesarean deliveries are limited, Nadir Sharawi, MD, of the University of Arkansas for Medical Sciences, Little Rock, and colleagues wrote.

courtesy University of Arkansas for Medical Sciences

DPE involves no injection of intrathecal drugs, and the potential advantages include easier translocation of epidural medications into the intrathecal space for improved analgesia, but the effects of DPE on the onset and reliability of surgical anesthesia remain unknown, they said.

In a study published in JAMA Network Open, the researchers randomized 70 women scheduled for cesarean delivery of singleton pregnancies to DPE and 70 to a standard epidural. The participants were aged 18 years and older, with a mean age of the 30.1 years; the study was conducted between April 2019 and October 2022 at a single center.

The primary outcome was the time to the loss of sharp sensation at T6, defined as “the start of epidural extension anesthesia (time zero on the stopwatch) to when the patient could no longer feel sharp sensation at T6 (assessed bilaterally at the midclavicular line),” the researchers wrote.

The onset time to surgical anesthesia was faster in the DPE group, compared with the standard group, with a median of 422 seconds versus 655 seconds.

A key secondary outcome was a composite measure of the quality of epidural anesthesia that included failure to achieve a T10 bilateral block preoperatively in the delivery room, failure to achieve a surgical block at T6 within 15 minutes of chloroprocaine administration, requirement for intraoperative analgesia, repeat neuraxial procedure, and conversion to general anesthesia. The composite rates of lower quality anesthesia were significantly less in the DPE group, compared with the standard group (15.7% vs. 36.3%; P = .007).

Additional secondary outcomes included maternal satisfaction and pain score during surgery, adverse events, opioid use in the first 24 hours, maternal vasopressor requirements, epidural block assessments, and neonatal outcomes. No significant differences in these outcomes were noted between the groups, and no instances of local anesthetic systemic toxicity or neurological complications were reported.

The findings were limited by several factors including the study population of women scheduled for cesarean delivery and not in labor, and the inability to detect less frequent complications such as post–dural-puncture headache and accidental dural puncture, the researchers noted.

In addition, the results may vary with the use of other combinations of local anesthetics and opioids. “Chloroprocaine was chosen in this study because of its ease of administration without the need for opioids and other additives along with the low risk of systemic toxic effects, which favors rapid administration for emergent cesarean delivery,” they wrote.

However, the results show an association between DPE within an hour of epidural extension for elective cesarean delivery and a faster onset of anesthesia, improved block quality, and a more favorable ratio of risks versus benefits, compared with the use of standard epidural, the researchers concluded.
 

No need for general anesthesia?

“There is controversy over whether the dural puncture epidural technique improves labor analgesia when compared to a standard epidural,” Dr. Shawari said in an interview. “However, there are limited data on whether the dural puncture epidural technique decreases the onset time to surgical anesthesia when compared to a standard epidural for cesarean delivery. This is important as a pre-existing epidural is commonly used to convert labor analgesia to surgical anesthesia in the setting of urgent cesarean delivery. A faster onset of epidural anesthesia could potentially avoid the need for general anesthesia in an emergency.”

The researchers were not surprised by the findings given their experience with performing dural puncture epidurals for labor analgesia, Dr. Shawari said. In those cases, DPE provided a faster onset when converting cesarean anesthesia, compared with a standard epidural.

The takeaway from the current study is that DPE also provided “a faster onset and improved quality of anesthesia when compared to standard epidural for elective cesarean delivery,” Dr. Shawari said. However, additional research is needed to confirm the findings for intrapartum cesarean delivery.
 

Progress in improving pain control

“Adequate pain control during cesarean delivery is incredibly important,” Catherine Albright, MD, a maternal-fetal medicine specialist at the University of Washington, Seattle, said in an interview. “Inadequate pain control leads to the need to provide additional intravenous medications or the need to be put under general anesthesia, which changes the birth experience and is more dangerous for the birthing person and the neonate.

courtesy University of Washington

“In my clinical experience, there are many times when patients do not have adequate pain control during a cesarean delivery,” said Dr. Albright, who was not involved in the current study. “I am pleased to see that there is research underway about how to best manage pain on labor and delivery, especially in the setting of conversion from labor anesthesia to cesarean anesthesia.”

The findings may have implications for clinical practice, said Dr. Albright. If the dural puncture epidural can improve cesarean anesthesia following an epidural during labor, rather than anesthesia provided for an elective cesarean), “then I believe it would reduce the number of patients who require additional pain medication, have a poor cesarean experience, and/or need to be put under general anesthesia.”

However, “as noted by the authors, additional research is needed to further determine possible risks and side effects from this technique, and also to ensure that it also works in the setting of labor, rather than for an elective cesarean,” Dr. Albright added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

Use of dural-puncture epidural (DPE) shortened the onset time to surgical anesthesia by approximately 3 minutes, compared with standard epidural in patients undergoing cesarean delivery, based on data from 140 individuals.

DPE, while not new, has become more popular as an option for initiating labor analgesia, but data comparing DPE with standard epidural in conversion to surgical anesthesia for cesarean deliveries are limited, Nadir Sharawi, MD, of the University of Arkansas for Medical Sciences, Little Rock, and colleagues wrote.

courtesy University of Arkansas for Medical Sciences

DPE involves no injection of intrathecal drugs, and the potential advantages include easier translocation of epidural medications into the intrathecal space for improved analgesia, but the effects of DPE on the onset and reliability of surgical anesthesia remain unknown, they said.

In a study published in JAMA Network Open, the researchers randomized 70 women scheduled for cesarean delivery of singleton pregnancies to DPE and 70 to a standard epidural. The participants were aged 18 years and older, with a mean age of the 30.1 years; the study was conducted between April 2019 and October 2022 at a single center.

The primary outcome was the time to the loss of sharp sensation at T6, defined as “the start of epidural extension anesthesia (time zero on the stopwatch) to when the patient could no longer feel sharp sensation at T6 (assessed bilaterally at the midclavicular line),” the researchers wrote.

The onset time to surgical anesthesia was faster in the DPE group, compared with the standard group, with a median of 422 seconds versus 655 seconds.

A key secondary outcome was a composite measure of the quality of epidural anesthesia that included failure to achieve a T10 bilateral block preoperatively in the delivery room, failure to achieve a surgical block at T6 within 15 minutes of chloroprocaine administration, requirement for intraoperative analgesia, repeat neuraxial procedure, and conversion to general anesthesia. The composite rates of lower quality anesthesia were significantly less in the DPE group, compared with the standard group (15.7% vs. 36.3%; P = .007).

Additional secondary outcomes included maternal satisfaction and pain score during surgery, adverse events, opioid use in the first 24 hours, maternal vasopressor requirements, epidural block assessments, and neonatal outcomes. No significant differences in these outcomes were noted between the groups, and no instances of local anesthetic systemic toxicity or neurological complications were reported.

The findings were limited by several factors including the study population of women scheduled for cesarean delivery and not in labor, and the inability to detect less frequent complications such as post–dural-puncture headache and accidental dural puncture, the researchers noted.

In addition, the results may vary with the use of other combinations of local anesthetics and opioids. “Chloroprocaine was chosen in this study because of its ease of administration without the need for opioids and other additives along with the low risk of systemic toxic effects, which favors rapid administration for emergent cesarean delivery,” they wrote.

However, the results show an association between DPE within an hour of epidural extension for elective cesarean delivery and a faster onset of anesthesia, improved block quality, and a more favorable ratio of risks versus benefits, compared with the use of standard epidural, the researchers concluded.
 

No need for general anesthesia?

“There is controversy over whether the dural puncture epidural technique improves labor analgesia when compared to a standard epidural,” Dr. Shawari said in an interview. “However, there are limited data on whether the dural puncture epidural technique decreases the onset time to surgical anesthesia when compared to a standard epidural for cesarean delivery. This is important as a pre-existing epidural is commonly used to convert labor analgesia to surgical anesthesia in the setting of urgent cesarean delivery. A faster onset of epidural anesthesia could potentially avoid the need for general anesthesia in an emergency.”

The researchers were not surprised by the findings given their experience with performing dural puncture epidurals for labor analgesia, Dr. Shawari said. In those cases, DPE provided a faster onset when converting cesarean anesthesia, compared with a standard epidural.

The takeaway from the current study is that DPE also provided “a faster onset and improved quality of anesthesia when compared to standard epidural for elective cesarean delivery,” Dr. Shawari said. However, additional research is needed to confirm the findings for intrapartum cesarean delivery.
 

Progress in improving pain control

“Adequate pain control during cesarean delivery is incredibly important,” Catherine Albright, MD, a maternal-fetal medicine specialist at the University of Washington, Seattle, said in an interview. “Inadequate pain control leads to the need to provide additional intravenous medications or the need to be put under general anesthesia, which changes the birth experience and is more dangerous for the birthing person and the neonate.

courtesy University of Washington

“In my clinical experience, there are many times when patients do not have adequate pain control during a cesarean delivery,” said Dr. Albright, who was not involved in the current study. “I am pleased to see that there is research underway about how to best manage pain on labor and delivery, especially in the setting of conversion from labor anesthesia to cesarean anesthesia.”

The findings may have implications for clinical practice, said Dr. Albright. If the dural puncture epidural can improve cesarean anesthesia following an epidural during labor, rather than anesthesia provided for an elective cesarean), “then I believe it would reduce the number of patients who require additional pain medication, have a poor cesarean experience, and/or need to be put under general anesthesia.”

However, “as noted by the authors, additional research is needed to further determine possible risks and side effects from this technique, and also to ensure that it also works in the setting of labor, rather than for an elective cesarean,” Dr. Albright added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

Use of dural-puncture epidural (DPE) shortened the onset time to surgical anesthesia by approximately 3 minutes, compared with standard epidural in patients undergoing cesarean delivery, based on data from 140 individuals.

DPE, while not new, has become more popular as an option for initiating labor analgesia, but data comparing DPE with standard epidural in conversion to surgical anesthesia for cesarean deliveries are limited, Nadir Sharawi, MD, of the University of Arkansas for Medical Sciences, Little Rock, and colleagues wrote.

courtesy University of Arkansas for Medical Sciences

DPE involves no injection of intrathecal drugs, and the potential advantages include easier translocation of epidural medications into the intrathecal space for improved analgesia, but the effects of DPE on the onset and reliability of surgical anesthesia remain unknown, they said.

In a study published in JAMA Network Open, the researchers randomized 70 women scheduled for cesarean delivery of singleton pregnancies to DPE and 70 to a standard epidural. The participants were aged 18 years and older, with a mean age of the 30.1 years; the study was conducted between April 2019 and October 2022 at a single center.

The primary outcome was the time to the loss of sharp sensation at T6, defined as “the start of epidural extension anesthesia (time zero on the stopwatch) to when the patient could no longer feel sharp sensation at T6 (assessed bilaterally at the midclavicular line),” the researchers wrote.

The onset time to surgical anesthesia was faster in the DPE group, compared with the standard group, with a median of 422 seconds versus 655 seconds.

A key secondary outcome was a composite measure of the quality of epidural anesthesia that included failure to achieve a T10 bilateral block preoperatively in the delivery room, failure to achieve a surgical block at T6 within 15 minutes of chloroprocaine administration, requirement for intraoperative analgesia, repeat neuraxial procedure, and conversion to general anesthesia. The composite rates of lower quality anesthesia were significantly less in the DPE group, compared with the standard group (15.7% vs. 36.3%; P = .007).

Additional secondary outcomes included maternal satisfaction and pain score during surgery, adverse events, opioid use in the first 24 hours, maternal vasopressor requirements, epidural block assessments, and neonatal outcomes. No significant differences in these outcomes were noted between the groups, and no instances of local anesthetic systemic toxicity or neurological complications were reported.

The findings were limited by several factors including the study population of women scheduled for cesarean delivery and not in labor, and the inability to detect less frequent complications such as post–dural-puncture headache and accidental dural puncture, the researchers noted.

In addition, the results may vary with the use of other combinations of local anesthetics and opioids. “Chloroprocaine was chosen in this study because of its ease of administration without the need for opioids and other additives along with the low risk of systemic toxic effects, which favors rapid administration for emergent cesarean delivery,” they wrote.

However, the results show an association between DPE within an hour of epidural extension for elective cesarean delivery and a faster onset of anesthesia, improved block quality, and a more favorable ratio of risks versus benefits, compared with the use of standard epidural, the researchers concluded.
 

No need for general anesthesia?

“There is controversy over whether the dural puncture epidural technique improves labor analgesia when compared to a standard epidural,” Dr. Shawari said in an interview. “However, there are limited data on whether the dural puncture epidural technique decreases the onset time to surgical anesthesia when compared to a standard epidural for cesarean delivery. This is important as a pre-existing epidural is commonly used to convert labor analgesia to surgical anesthesia in the setting of urgent cesarean delivery. A faster onset of epidural anesthesia could potentially avoid the need for general anesthesia in an emergency.”

The researchers were not surprised by the findings given their experience with performing dural puncture epidurals for labor analgesia, Dr. Shawari said. In those cases, DPE provided a faster onset when converting cesarean anesthesia, compared with a standard epidural.

The takeaway from the current study is that DPE also provided “a faster onset and improved quality of anesthesia when compared to standard epidural for elective cesarean delivery,” Dr. Shawari said. However, additional research is needed to confirm the findings for intrapartum cesarean delivery.
 

Progress in improving pain control

“Adequate pain control during cesarean delivery is incredibly important,” Catherine Albright, MD, a maternal-fetal medicine specialist at the University of Washington, Seattle, said in an interview. “Inadequate pain control leads to the need to provide additional intravenous medications or the need to be put under general anesthesia, which changes the birth experience and is more dangerous for the birthing person and the neonate.

courtesy University of Washington

“In my clinical experience, there are many times when patients do not have adequate pain control during a cesarean delivery,” said Dr. Albright, who was not involved in the current study. “I am pleased to see that there is research underway about how to best manage pain on labor and delivery, especially in the setting of conversion from labor anesthesia to cesarean anesthesia.”

The findings may have implications for clinical practice, said Dr. Albright. If the dural puncture epidural can improve cesarean anesthesia following an epidural during labor, rather than anesthesia provided for an elective cesarean), “then I believe it would reduce the number of patients who require additional pain medication, have a poor cesarean experience, and/or need to be put under general anesthesia.”

However, “as noted by the authors, additional research is needed to further determine possible risks and side effects from this technique, and also to ensure that it also works in the setting of labor, rather than for an elective cesarean,” Dr. Albright added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Albright had no financial conflicts to disclose.

The Food and Drug Administration has approved the first oral agent specifically for postpartum depression, a condition that affects an estimated one in seven mothers in the United States.

The pill, zuranolone (Zurzuvae), is a neuroactive steroid that acts on GABAA receptors in the brain responsible for regulating mood, arousal, behavior, and cognition, according to Biogen, which, along with Sage Therapeutics, developed the product. The recommended dose for Zurzuvae is 50 mg taken once daily for 14 days, in the evening with a fatty meal, according to the FDA.

Olivier Le Moal/Getty Images

Postpartum depression often goes undiagnosed and untreated. Many mothers are hesitant to reveal their symptoms to family and clinicians, fearing they’ll be judged on their parenting. A 2017 study found that suicide accounted for roughly 5% of perinatal deaths among women in Canada, with most of those deaths occurring in the first 3 months in the year after giving birth.

“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness – even, in severe cases, thoughts of harming themselves or their child. And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA’s Center for Drug Evaluation and Research, said in a statement about the approval. “Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”

The other approved therapy for postpartum depression is the intravenous agent brexanolone (Zulresso; Sage). But the product requires prolonged infusions in hospital settings and costs $34,000.

FDA approval of Zurzuvae was based in part on data reported in a 2023 study in the American Journal of Psychiatry, which showed that the drug led to significantly greater improvement in depressive symptoms at 15 days compared with the placebo group. Improvements were observed on day 3, the earliest assessment, and were sustained at all subsequent visits during the treatment and follow-up period (through day 42).

Patients with anxiety who received the active drug experienced improvement in related symptoms compared with the patients who received a placebo.

The most common adverse events reported in the trial were somnolence and headaches. Weight gain, sexual dysfunction, withdrawal symptoms, and increased suicidal ideation or behavior were not observed.

The packaging for Zurzuvae will include a boxed warning noting that the drug can affect a user’s ability to drive and perform other potentially hazardous activities, possibly without their knowledge of the impairment, the FDA said. As a result, people who use Zurzuvae should not drive or operate heavy machinery for at least 12 hours after taking the pill.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved the first oral agent specifically for postpartum depression, a condition that affects an estimated one in seven mothers in the United States.

The pill, zuranolone (Zurzuvae), is a neuroactive steroid that acts on GABAA receptors in the brain responsible for regulating mood, arousal, behavior, and cognition, according to Biogen, which, along with Sage Therapeutics, developed the product. The recommended dose for Zurzuvae is 50 mg taken once daily for 14 days, in the evening with a fatty meal, according to the FDA.

Olivier Le Moal/Getty Images

Postpartum depression often goes undiagnosed and untreated. Many mothers are hesitant to reveal their symptoms to family and clinicians, fearing they’ll be judged on their parenting. A 2017 study found that suicide accounted for roughly 5% of perinatal deaths among women in Canada, with most of those deaths occurring in the first 3 months in the year after giving birth.

“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness – even, in severe cases, thoughts of harming themselves or their child. And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA’s Center for Drug Evaluation and Research, said in a statement about the approval. “Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”

The other approved therapy for postpartum depression is the intravenous agent brexanolone (Zulresso; Sage). But the product requires prolonged infusions in hospital settings and costs $34,000.

FDA approval of Zurzuvae was based in part on data reported in a 2023 study in the American Journal of Psychiatry, which showed that the drug led to significantly greater improvement in depressive symptoms at 15 days compared with the placebo group. Improvements were observed on day 3, the earliest assessment, and were sustained at all subsequent visits during the treatment and follow-up period (through day 42).

Patients with anxiety who received the active drug experienced improvement in related symptoms compared with the patients who received a placebo.

The most common adverse events reported in the trial were somnolence and headaches. Weight gain, sexual dysfunction, withdrawal symptoms, and increased suicidal ideation or behavior were not observed.

The packaging for Zurzuvae will include a boxed warning noting that the drug can affect a user’s ability to drive and perform other potentially hazardous activities, possibly without their knowledge of the impairment, the FDA said. As a result, people who use Zurzuvae should not drive or operate heavy machinery for at least 12 hours after taking the pill.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved the first oral agent specifically for postpartum depression, a condition that affects an estimated one in seven mothers in the United States.

The pill, zuranolone (Zurzuvae), is a neuroactive steroid that acts on GABAA receptors in the brain responsible for regulating mood, arousal, behavior, and cognition, according to Biogen, which, along with Sage Therapeutics, developed the product. The recommended dose for Zurzuvae is 50 mg taken once daily for 14 days, in the evening with a fatty meal, according to the FDA.

Olivier Le Moal/Getty Images

Postpartum depression often goes undiagnosed and untreated. Many mothers are hesitant to reveal their symptoms to family and clinicians, fearing they’ll be judged on their parenting. A 2017 study found that suicide accounted for roughly 5% of perinatal deaths among women in Canada, with most of those deaths occurring in the first 3 months in the year after giving birth.

“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness – even, in severe cases, thoughts of harming themselves or their child. And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA’s Center for Drug Evaluation and Research, said in a statement about the approval. “Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”

The other approved therapy for postpartum depression is the intravenous agent brexanolone (Zulresso; Sage). But the product requires prolonged infusions in hospital settings and costs $34,000.

FDA approval of Zurzuvae was based in part on data reported in a 2023 study in the American Journal of Psychiatry, which showed that the drug led to significantly greater improvement in depressive symptoms at 15 days compared with the placebo group. Improvements were observed on day 3, the earliest assessment, and were sustained at all subsequent visits during the treatment and follow-up period (through day 42).

Patients with anxiety who received the active drug experienced improvement in related symptoms compared with the patients who received a placebo.

The most common adverse events reported in the trial were somnolence and headaches. Weight gain, sexual dysfunction, withdrawal symptoms, and increased suicidal ideation or behavior were not observed.

The packaging for Zurzuvae will include a boxed warning noting that the drug can affect a user’s ability to drive and perform other potentially hazardous activities, possibly without their knowledge of the impairment, the FDA said. As a result, people who use Zurzuvae should not drive or operate heavy machinery for at least 12 hours after taking the pill.

A version of this article first appeared on Medscape.com.

SEATTLE – A family of blockbuster drugs for managing blood glucose – and now for promoting weight loss – has been linked to exacerbation of macular disease that frequently accompanies diabetes, new data show.

Two studies presented at the annual meeting of the American Society of Retina Specialists (ASRS) have found that use of injectable agonists of glucagonlike peptide-1 (GLP1) appears to hasten the progression of diabetic retinopathy and diabetic macular edema (DME).

Clinicians should be aware of these effects of GLP-1 inhibitors to ensure appropriate monitoring of patients for the possibility that retinopathy may accelerate, according to Ehsan Rahimy, MD, an adjunct clinical professor at Stanford (Calif.) University, and colleagues.

Dr. Rahimy presented results of a retrospective study of retinopathy progression in patients taking either GLP-1 agonists or sodium-glucose transporter-2 (SGLT-2) inhibitors, also known as gliflozins. “When we looked at the conversion to proliferative disease, you can see it was statistically higher in the GLP-1 group at all time points,” he said.

GLP-1 agonists can promote considerable weight loss in patients with and without diabetes. Moreover, the finding that gliflozins improve cardiovascular and renal function in patients with type 2 diabetes has accelerated the use of these agents for blood glucose control.

Using a repository of data from more than 13,500 people taking either of the two kinds of medication, the researchers looked for conversion of diabetic eye disease to proliferative diabetic retinopathy (PDR) or DME. Secondary outcomes were the need for intravitreal injections, panretinal photocoagulation (PRP), or pars plana vitrectomy (PPV).

Propensity score matching for age, sex, race, ethnicity, and baseline hemoglobin A1c resulted in the inclusion of 5,446 participants in each treatment group. After matching, the mean age of participants in either group was 64 years, and the mean A1c was 8.5%. Slightly more than half the participants were insulin-dependent.

Patients taking GLP-1 inhibitors had higher rates of conversion to PDR than those taking gliflozins at 3 years (6% vs. 4%; P < .01), the researchers found. Nearly 25% of those taking a GLP-1 agonist had progressed to DME after 3 years, compared with 18% of those taking a gliflozin.

People in the group taking GLP-1 inhibitors also had a greater need for interventions than those on a gliflozin; 8% vs. roughly 6%, respectively, required intravitreal injections, Dr. Rahimy reported. Similar trends were noted for need for PRP and PPV, he added, although the absolute numbers of patients were small.
 

Albiglutide the key culprit?

In other research reported at the meeting, a meta-analysis of data collected in 93 randomized clinical trials of the seven currently available GLP-1 agonists found only albiglutide was associated with diabetic retinopathy to a statistically significant degree. Compared with placebo, albiglutide more than doubled the risk for early-stage diabetic retinopathy (relative risk 2.18; 95% confidence interval, 1.01-4.67; P = .05).

Other GLP-1 agonists evaluated in the meta-analysis included semaglutide, tirzepatide, dulaglutide, exenatide, liraglutide, and lixisenatide. These findings were reported in a poster presented at the meeting by Ishani Kapoor, MD candidate, Drexel University, Philadelphia.

“The strength of these effects depends on the specific GLP-1 receptor agonist used, patient-specific clinical characteristics, and demographics,” Ms. Kapoor and coauthors reported. “Further studies are needed to clarify the patient populations that would benefit from GLP-1 receptor agonists and those at risk for [the] development of additional ocular damage.”
 

What causes progression?

Whether worsening of retinopathy stems from rapid weight loss and acute reductions in concentrations of blood glucose or is a direct effect of GLP-1 agonists on the eye is unclear.

“That rapid reduction is thought to play some role,” Dr. Rahimy said. “But if you actually look out there in the basic science literature, it’s suggested that there are direct effects of these medications on the retina too. That being said, it’s suggested that they may be protective to the retina. And I think that’s where we’ve gotten a lot of mixed signals in our community between what we’ve seen on the basic science side vs. what we’re seeing on the real-world side.”

The study was independently funded. Dr. Rahimy reports consultancies or speakerships with AbbVie, Allergan, Apellis, Carl Zeiss, Genentech, and Google, and research support from Regeneron. Ms. Kapoor reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

SEATTLE – A family of blockbuster drugs for managing blood glucose – and now for promoting weight loss – has been linked to exacerbation of macular disease that frequently accompanies diabetes, new data show.

Two studies presented at the annual meeting of the American Society of Retina Specialists (ASRS) have found that use of injectable agonists of glucagonlike peptide-1 (GLP1) appears to hasten the progression of diabetic retinopathy and diabetic macular edema (DME).

Clinicians should be aware of these effects of GLP-1 inhibitors to ensure appropriate monitoring of patients for the possibility that retinopathy may accelerate, according to Ehsan Rahimy, MD, an adjunct clinical professor at Stanford (Calif.) University, and colleagues.

Dr. Rahimy presented results of a retrospective study of retinopathy progression in patients taking either GLP-1 agonists or sodium-glucose transporter-2 (SGLT-2) inhibitors, also known as gliflozins. “When we looked at the conversion to proliferative disease, you can see it was statistically higher in the GLP-1 group at all time points,” he said.

GLP-1 agonists can promote considerable weight loss in patients with and without diabetes. Moreover, the finding that gliflozins improve cardiovascular and renal function in patients with type 2 diabetes has accelerated the use of these agents for blood glucose control.

Using a repository of data from more than 13,500 people taking either of the two kinds of medication, the researchers looked for conversion of diabetic eye disease to proliferative diabetic retinopathy (PDR) or DME. Secondary outcomes were the need for intravitreal injections, panretinal photocoagulation (PRP), or pars plana vitrectomy (PPV).

Propensity score matching for age, sex, race, ethnicity, and baseline hemoglobin A1c resulted in the inclusion of 5,446 participants in each treatment group. After matching, the mean age of participants in either group was 64 years, and the mean A1c was 8.5%. Slightly more than half the participants were insulin-dependent.

Patients taking GLP-1 inhibitors had higher rates of conversion to PDR than those taking gliflozins at 3 years (6% vs. 4%; P < .01), the researchers found. Nearly 25% of those taking a GLP-1 agonist had progressed to DME after 3 years, compared with 18% of those taking a gliflozin.

People in the group taking GLP-1 inhibitors also had a greater need for interventions than those on a gliflozin; 8% vs. roughly 6%, respectively, required intravitreal injections, Dr. Rahimy reported. Similar trends were noted for need for PRP and PPV, he added, although the absolute numbers of patients were small.
 

Albiglutide the key culprit?

In other research reported at the meeting, a meta-analysis of data collected in 93 randomized clinical trials of the seven currently available GLP-1 agonists found only albiglutide was associated with diabetic retinopathy to a statistically significant degree. Compared with placebo, albiglutide more than doubled the risk for early-stage diabetic retinopathy (relative risk 2.18; 95% confidence interval, 1.01-4.67; P = .05).

Other GLP-1 agonists evaluated in the meta-analysis included semaglutide, tirzepatide, dulaglutide, exenatide, liraglutide, and lixisenatide. These findings were reported in a poster presented at the meeting by Ishani Kapoor, MD candidate, Drexel University, Philadelphia.

“The strength of these effects depends on the specific GLP-1 receptor agonist used, patient-specific clinical characteristics, and demographics,” Ms. Kapoor and coauthors reported. “Further studies are needed to clarify the patient populations that would benefit from GLP-1 receptor agonists and those at risk for [the] development of additional ocular damage.”
 

What causes progression?

Whether worsening of retinopathy stems from rapid weight loss and acute reductions in concentrations of blood glucose or is a direct effect of GLP-1 agonists on the eye is unclear.

“That rapid reduction is thought to play some role,” Dr. Rahimy said. “But if you actually look out there in the basic science literature, it’s suggested that there are direct effects of these medications on the retina too. That being said, it’s suggested that they may be protective to the retina. And I think that’s where we’ve gotten a lot of mixed signals in our community between what we’ve seen on the basic science side vs. what we’re seeing on the real-world side.”

The study was independently funded. Dr. Rahimy reports consultancies or speakerships with AbbVie, Allergan, Apellis, Carl Zeiss, Genentech, and Google, and research support from Regeneron. Ms. Kapoor reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

SEATTLE – A family of blockbuster drugs for managing blood glucose – and now for promoting weight loss – has been linked to exacerbation of macular disease that frequently accompanies diabetes, new data show.

Two studies presented at the annual meeting of the American Society of Retina Specialists (ASRS) have found that use of injectable agonists of glucagonlike peptide-1 (GLP1) appears to hasten the progression of diabetic retinopathy and diabetic macular edema (DME).

Clinicians should be aware of these effects of GLP-1 inhibitors to ensure appropriate monitoring of patients for the possibility that retinopathy may accelerate, according to Ehsan Rahimy, MD, an adjunct clinical professor at Stanford (Calif.) University, and colleagues.

Dr. Rahimy presented results of a retrospective study of retinopathy progression in patients taking either GLP-1 agonists or sodium-glucose transporter-2 (SGLT-2) inhibitors, also known as gliflozins. “When we looked at the conversion to proliferative disease, you can see it was statistically higher in the GLP-1 group at all time points,” he said.

GLP-1 agonists can promote considerable weight loss in patients with and without diabetes. Moreover, the finding that gliflozins improve cardiovascular and renal function in patients with type 2 diabetes has accelerated the use of these agents for blood glucose control.

Using a repository of data from more than 13,500 people taking either of the two kinds of medication, the researchers looked for conversion of diabetic eye disease to proliferative diabetic retinopathy (PDR) or DME. Secondary outcomes were the need for intravitreal injections, panretinal photocoagulation (PRP), or pars plana vitrectomy (PPV).

Propensity score matching for age, sex, race, ethnicity, and baseline hemoglobin A1c resulted in the inclusion of 5,446 participants in each treatment group. After matching, the mean age of participants in either group was 64 years, and the mean A1c was 8.5%. Slightly more than half the participants were insulin-dependent.

Patients taking GLP-1 inhibitors had higher rates of conversion to PDR than those taking gliflozins at 3 years (6% vs. 4%; P < .01), the researchers found. Nearly 25% of those taking a GLP-1 agonist had progressed to DME after 3 years, compared with 18% of those taking a gliflozin.

People in the group taking GLP-1 inhibitors also had a greater need for interventions than those on a gliflozin; 8% vs. roughly 6%, respectively, required intravitreal injections, Dr. Rahimy reported. Similar trends were noted for need for PRP and PPV, he added, although the absolute numbers of patients were small.
 

Albiglutide the key culprit?

In other research reported at the meeting, a meta-analysis of data collected in 93 randomized clinical trials of the seven currently available GLP-1 agonists found only albiglutide was associated with diabetic retinopathy to a statistically significant degree. Compared with placebo, albiglutide more than doubled the risk for early-stage diabetic retinopathy (relative risk 2.18; 95% confidence interval, 1.01-4.67; P = .05).

Other GLP-1 agonists evaluated in the meta-analysis included semaglutide, tirzepatide, dulaglutide, exenatide, liraglutide, and lixisenatide. These findings were reported in a poster presented at the meeting by Ishani Kapoor, MD candidate, Drexel University, Philadelphia.

“The strength of these effects depends on the specific GLP-1 receptor agonist used, patient-specific clinical characteristics, and demographics,” Ms. Kapoor and coauthors reported. “Further studies are needed to clarify the patient populations that would benefit from GLP-1 receptor agonists and those at risk for [the] development of additional ocular damage.”
 

What causes progression?

Whether worsening of retinopathy stems from rapid weight loss and acute reductions in concentrations of blood glucose or is a direct effect of GLP-1 agonists on the eye is unclear.

“That rapid reduction is thought to play some role,” Dr. Rahimy said. “But if you actually look out there in the basic science literature, it’s suggested that there are direct effects of these medications on the retina too. That being said, it’s suggested that they may be protective to the retina. And I think that’s where we’ve gotten a lot of mixed signals in our community between what we’ve seen on the basic science side vs. what we’re seeing on the real-world side.”

The study was independently funded. Dr. Rahimy reports consultancies or speakerships with AbbVie, Allergan, Apellis, Carl Zeiss, Genentech, and Google, and research support from Regeneron. Ms. Kapoor reports no relevant financial relationships.

A version of this article appeared on Medscape.com.

A new lawsuit from a woman with type 2 diabetes alleges that the makers of the drugs Ozempic and Mounjaro did not provide adequate warnings for the severity of stomach problems caused by the popular medicines.

The two drugs, which are Food and Drug Administration approved to treat type 2 diabetes, have become well known for their weight loss properties. Ozempic is made by Danish drug maker Novo Nordisk, and Mounjaro is made by Indiana-based Eli Lilly and Co.

In the lawsuit, Jaclyn Bjorklund, 44, of Louisiana, asserts that she was “severely injured” after using Ozempic and Mounjaro and that the pharmaceutical companies failed to disclose the drugs’ risk of causing vomiting and diarrhea due to inflammation of the stomach lining, as well as the risk of gastroparesis.

The prescribing labels for Mounjaro and Ozempic state that each “delays gastric emptying” and warn of the risk of severe gastrointestinal adverse reactions. The prescribing labels for both drugs state that the most common side effects include vomiting, diarrhea, and stomach pain. The Ozempic label does not mention gastroparesis, and the Mounjaro label states that the drug has not been studied in people with the condition and is therefore not recommended for people who have it. 

Ms. Bjorklund has not been diagnosed with gastroparesis, but her symptoms are “indicative of” the condition, her lawyer, Paul Pennock, told NBC News.

Ms. Bjorklund used Ozempic for more than 1 year, and in July 2023 switched to Mounjaro, the lawsuit states. The document, posted on her law firm’s website, details that using the drugs resulted in “severe vomiting, stomach pain, gastrointestinal burning, being hospitalized for stomach issues on several occasions including visits to the emergency room, [and] teeth falling out due to excessive vomiting, requiring additional medications to alleviate her excessive vomiting, and throwing up whole food hours after eating.”

Novo Nordisk spokesperson Natalia Salomao told NBC News that patient safety is “of utmost importance to Novo Nordisk,” and she also noted that gastroparesis is a known risk for people with diabetes. The Food and Drug Administration declined to comment on the case, and Eli Lilly did not immediately respond to a request for comment, NBC News reported.
 

A version of this article first appeared on WebMD.com.

A new lawsuit from a woman with type 2 diabetes alleges that the makers of the drugs Ozempic and Mounjaro did not provide adequate warnings for the severity of stomach problems caused by the popular medicines.

The two drugs, which are Food and Drug Administration approved to treat type 2 diabetes, have become well known for their weight loss properties. Ozempic is made by Danish drug maker Novo Nordisk, and Mounjaro is made by Indiana-based Eli Lilly and Co.

In the lawsuit, Jaclyn Bjorklund, 44, of Louisiana, asserts that she was “severely injured” after using Ozempic and Mounjaro and that the pharmaceutical companies failed to disclose the drugs’ risk of causing vomiting and diarrhea due to inflammation of the stomach lining, as well as the risk of gastroparesis.

The prescribing labels for Mounjaro and Ozempic state that each “delays gastric emptying” and warn of the risk of severe gastrointestinal adverse reactions. The prescribing labels for both drugs state that the most common side effects include vomiting, diarrhea, and stomach pain. The Ozempic label does not mention gastroparesis, and the Mounjaro label states that the drug has not been studied in people with the condition and is therefore not recommended for people who have it. 

Ms. Bjorklund has not been diagnosed with gastroparesis, but her symptoms are “indicative of” the condition, her lawyer, Paul Pennock, told NBC News.

Ms. Bjorklund used Ozempic for more than 1 year, and in July 2023 switched to Mounjaro, the lawsuit states. The document, posted on her law firm’s website, details that using the drugs resulted in “severe vomiting, stomach pain, gastrointestinal burning, being hospitalized for stomach issues on several occasions including visits to the emergency room, [and] teeth falling out due to excessive vomiting, requiring additional medications to alleviate her excessive vomiting, and throwing up whole food hours after eating.”

Novo Nordisk spokesperson Natalia Salomao told NBC News that patient safety is “of utmost importance to Novo Nordisk,” and she also noted that gastroparesis is a known risk for people with diabetes. The Food and Drug Administration declined to comment on the case, and Eli Lilly did not immediately respond to a request for comment, NBC News reported.
 

A version of this article first appeared on WebMD.com.

A new lawsuit from a woman with type 2 diabetes alleges that the makers of the drugs Ozempic and Mounjaro did not provide adequate warnings for the severity of stomach problems caused by the popular medicines.

The two drugs, which are Food and Drug Administration approved to treat type 2 diabetes, have become well known for their weight loss properties. Ozempic is made by Danish drug maker Novo Nordisk, and Mounjaro is made by Indiana-based Eli Lilly and Co.

In the lawsuit, Jaclyn Bjorklund, 44, of Louisiana, asserts that she was “severely injured” after using Ozempic and Mounjaro and that the pharmaceutical companies failed to disclose the drugs’ risk of causing vomiting and diarrhea due to inflammation of the stomach lining, as well as the risk of gastroparesis.

The prescribing labels for Mounjaro and Ozempic state that each “delays gastric emptying” and warn of the risk of severe gastrointestinal adverse reactions. The prescribing labels for both drugs state that the most common side effects include vomiting, diarrhea, and stomach pain. The Ozempic label does not mention gastroparesis, and the Mounjaro label states that the drug has not been studied in people with the condition and is therefore not recommended for people who have it. 

Ms. Bjorklund has not been diagnosed with gastroparesis, but her symptoms are “indicative of” the condition, her lawyer, Paul Pennock, told NBC News.

Ms. Bjorklund used Ozempic for more than 1 year, and in July 2023 switched to Mounjaro, the lawsuit states. The document, posted on her law firm’s website, details that using the drugs resulted in “severe vomiting, stomach pain, gastrointestinal burning, being hospitalized for stomach issues on several occasions including visits to the emergency room, [and] teeth falling out due to excessive vomiting, requiring additional medications to alleviate her excessive vomiting, and throwing up whole food hours after eating.”

Novo Nordisk spokesperson Natalia Salomao told NBC News that patient safety is “of utmost importance to Novo Nordisk,” and she also noted that gastroparesis is a known risk for people with diabetes. The Food and Drug Administration declined to comment on the case, and Eli Lilly did not immediately respond to a request for comment, NBC News reported.
 

A version of this article first appeared on WebMD.com.