Data shows surge in in new GLP-1RA prescriptions for obesity without type 2 diabetes

Embargoed for release until 5:00 p.m. ET on Monday 22 July 2024    
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Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.    
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1. Data shows surge in in new GLP-1RA prescriptions for obesity without type 2 diabetes

Semaglutide was, by far, the most frequently prescribed GLP-1RA in 2023

Abstract: https://www.acpjournals.org/doi/10.7326/M24-0019   

URL goes live when the embargo lifts    

A nationwide study found a marked increase in new GLP-1RA prescriptions over the last decade, particularly since 2020. Semaglutide was the most prescribed GLP-1RA, by far, in 2023. Notably, the proportion of new users with type 2 diabetes decreased whereas prescriptions among those with obesity or relevant comorbid conditions but without T2D spiked. According to the study authors, the high prevalence of obesity and the increasing demand for GLP-1RA prescriptions for obesity could contribute to drug shortages and may worsen existing racial and ethnic disparities in drug access. The brief research report is published in Annals of Internal Medicine.

Researchers from the Perelman School of Medicine at the University of Pennsylvania and Cedars-Sinai studied data from TriNetX, a federated health research network with records for 45 million individuals in the United States, to delineate the annual trend in new prescriptions of GLP-1RAs between 2011 and 2023, categorized by the presence of diabetes and comorbid conditions related to diabetes or obesity. New prescriptions were defined as users who received GLP-1RAs for the first time in their records in the TrinetX database. The data showed that of the 1 million new GLP-1RA users identified during the study timeframe, users were disproportionately female, non-Hispanic White, and had a BMI of 30 kg/m2 or greater. During the same period, there was a 2-fold increase in the proportions of users without type 2 diabetes but with a BMI of 30 kg/m2 or greater, or in those with a BMI of 27 to 30 kg/m2 and an obesity-related comorbid condition. Additionally, the proportion of users without FDA-approved indications increased from 0.21% in 2019 to 0.37% in 2023. In 2019, semaglutide and liraglutide constituted 31.4% and 35.3% of all new GLP-1RA prescriptions, respectively. In 2023, these proportions increased to 88.1% for semaglutide, and decreased to 10.3% for liraglutide.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with one of the corresponding authors, please contact Shishira Sreenivas at Shishira.Sreenivas@cshs.org

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2. ACP Calls for Evidence-Based Public Health Approach to Cannabis Regulation

Abstract: https://www.acpjournals.org/doi/10.7326/M24-0638            

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A public health approach is necessary to address the legal, medical, and social complexities of cannabis use, says the American College of Physicians (ACP) in a new policy paper, “Regulatory Framework for Cannabis: A Position Paper from the American College of Physicians.”  In the paper, ACP issues recommendations to policymakers on adopting a public health approach to prevent and control adverse cannabis-related health outcomes. The policy paper is published in Annals of Internal Medicine.

Among the recommendations, ACP supports rigorous research into the health effects, potential therapeutic uses, and the impact of legalization on cannabis use. Additionally, ACP calls for the decriminalization of possession of small amounts of cannabis for personal use to help address systemic inequities and promote a treatment-focused alternative to criminal penalties for substance use disorders. The policy paper goes on to outline a public health approach to controlling cannabis in jurisdictions where it is already legal. ACP also calls for insurance coverage of treatment for cannabis use disorder and incorporating information about cannabis into medical education.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with someone from ACP, please contact Jacqueline Blaser at jblaser@acponline.org.

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3. For clinicians, diagnostic criteria for obesity remains elusive

BMI a useful clinical tool, but racial and ethnic disparities must be addressed

Abstract: https://www.acpjournals.org/doi/10.7326/M23-3391     

Abstract: https://www.acpjournals.org/doi/10.7326/M24-0161     

Editorial: https://www.acpjournals.org/doi/10.7326/M24-0884     

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Obesity now affects 2 in 5 U.S. adults, making it one of the most important public health problems facing society. However, finding an accurate way to identify obesity in individuals remains challenging given the very diverse U.S. patient population. In two new papers published in Annals of Internal Medicine, social justice and obesity experts weigh in on the Body Mass Index and discuss its advantages and challenges as a measure of obesity, particularly in different racial and ethnic groups, and how this influences perceptions and patient care.

Authors from New York University School of Global Public Health suggest that BMI (weight in kilograms divided by the square of height in meters) remains useful for identifying obesity. While clinical decisions can be enhanced with additional measures, such as waist circumference and weight changes over time, BMI is strongly associated with indicators of cardiovascular risk, is low cost, and easy to measure in the clinical encounter. And among healthy persons who do not smoke, studies also show that the relationship between BMI and mortality is nearly identical among Black persons, White persons, and Asian Americans in relative terms-- and because BMI data are readily available across populations and time, it provides a useful metric by which to comprehend and quantify the ramifications of structural racism and discrimination for population health. This enables researchers to gain deeper insights into the influence of systemic factors—including inequities in resource allocation, educational access, housing security, dietary options, and health care quality—on health outcomes and to develop efficacious interventions to mitigate health disparities.

Authors from Harvard Medical School, Massachusetts General Hospital, MGH Weight Center suggest, however, the implications of universal thresholds to define obesity may results in health disparities as obesity manifests differently in different populations. The need for different BMI thresholds to define obesity in Asian populations offer lessons that may help to address existing disparities in health care. In 2004, the World Health Organization (WHO) suggested a lower BMI cutoff for many Asian populations because of their higher tendency toward central adiposity and risk for type 2 diabetes. While these changes were clinically important, Asian populations are not monolithic and organizations should acknowledge these BMI thresholds as only temporary placeholders until when we can establish whether even more specific thresholds are needed to define obesity across different Asian ethnic subpopulations. Authors advocate for more funding to research how to replace proxy values with better evidence-based thresholds. The authors say that with recent pushes toward disaggregated data and personalized medicine, increasing granularity for Asian Americans could potentially pave the way for similar efforts among all racial and ethnic groups, making diagnosis of obesity more accurate, tailored, and equitable.

An accompanying editorial from Annals of Internal Medicine notes that consensus on how obesity should be defined remains elusive and argues that beyond diagnostic challenges, focusing on obesity exclusively as a disease rather than a broader, more inclusive construct may have unintended consequences—including reinforcing the weight bias in our current healthcare reimbursement system. The healthcare community takes treating similar health risk factors including hypertension and high cholesterol seriously even before these result in disease complications but health insurers, including Medicare, apply a higher bar when it comes to covering obesity treatment. Because obesity has multiple genetic, social, cultural, environmental and behavioral contributors, addressing obesity requires that clinicians have the time and space to get to know their patients as people. This is particularly imperative now for many reasons, including because of the increasing demand for new highly effective weight loss agents. Equitable dissemination of these treatments will require clinicians to be able to make nuanced clinical decisions based on contributors to an individual patient's obesity and the health risk it poses, and not just whether it meets a panel's definition of "disease." The author suggests that obesity should be recognized as a serious health threat and “pandemic,” and as such, clinical education about obesity needs to be a priority in medical school and residency training.

Media contacts: For an embargoed PDF or to speak with editorialist, Christina Wee, MD, MPH, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author for the BMI paper, Adolfo G. Cuevas, PhD, please email, Rachel Harrison at rachel.harrison@nyu.edu. To speak with the author of the BMI thresholds and Asian population paper, Fatima Cody Stanford, MD, MPH, MPA, MBA, MGH, please email Marissa Lynn Hankins at mhankins@mgb.org.

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4. Co-use of CYP2D6-metabolized opioids and antidepressants associated with adverse events in older nursing home patients

Abstract: https://www.acpjournals.org/doi/10.7326/M23-3109     

URL goes live when the embargo lifts     

A target trial emulation study found that concomitant use of CYP2D6-metabolized opioids (hydrocodone, codeine, tramadol, and oxycodone) with antidepressants was associated with adverse outcomes among older nursing home residents. This is important because opioids metabolized by the cytochrome P450 (CYP) 2D6 (CYP2D6) enzyme are commonly prescribed among older adults, including those living in nursing homes. In fact, more than one-third of Medicare nursing home (NH) residents (the population studied in this trial) with chronic pain received prescription opioids concurrently with antidepressants between 2011 and 2015. The findings are published in Annals of Internal Medicine.

Researchers from The Ohio State University used a target trial emulation design to investigate the associations of concomitant use of CYP2D6-metabolized opioids and antidepressants with clinical outcomes and opioid-related adverse events (ORAEs) in older Medicare recipients. The authors used a 100% NH sample linked to Medicare claims for long-term residents aged 65 years and older receiving CYP2D6-metabolized opioids with a disease indication for antidepressant use and looked for worsening pain, physical function, and depression from baseline and incident rates of pain-related hospitalizations and emergency department (ED) visits, opioid use disorder (OUD), and opioid overdose. They found that the use of CYP2D6-metabolized opioids concomitantly with CYP2D6-inhibiting (vs. CYP2D6-neutral) antidepressants was associated with a higher risk for worsening pain and higher incidence rates for pain-related hospitalization, pain-related ED visit, and OUD, with no difference in physical function, depression, and OD. According to the authors, these findings suggest that when co-use of opioids and antidepressants is clinically needed, selecting CYP2D6-neutral antidepressants (such as citalopram and sertraline) may provide better or equal clinical and adverse outcomes.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. To speak with the corresponding author Yu-Jung Jenny Wei, PhD, please contact Brittany McClasky at mcclaskey.25@osu.edu.

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