This month's issue of Clinical Therapeutics highlights the topic of obesity as a public health issue to which we, as a medical community and society, need to dramatically change our approach. We have curated a collection of commentaries and conversations with several experts in the field of obesity treatment, prevention, and advocacy. The guest contributors make a compelling argument for the classification of obesity as a disease. I offer reasons as to why obesity constitutes a public health emergency and how the current response is woefully insufficient compared to the magnitude of the problem.

The burden of obesity in the United States is staggering. In 2018, the prevalence of obesity (defined as a body mass index [BMI] of >30 kg/m2) in the US adult population (aged >18 years) was 42.4%, with almost 10% of cases classified as severe (BMI >40 kg/m2). With a US adult population of ~270 million in 2020, these statistics translate to >100 million with obesity and 25 million with severe obesity. This prevalence contrasts with those of some other common diseases about which our public health response and attitudes are vastly different: cancer, 1.7 million new cases in 2017; myocardial infarction, 805,000; and coronary artery disease, 6.7% of the adult population., In 2019, the National Institutes of Health (NIH) spent $6 billion in annual funding to support research on the treatment and prevention of cancer and $1.4 billion on cardiovascular disease; obesity funding was only $1.1 billion.5National Institutes of Health (NIH)
Estimates of Funding for Various Research, Condition, and Disease Categories. There is a dedicated institute at the NIH for cancer, and cardiovascular disease is a major pillar of another. There is no institute for obesity research; there is not even an office for obesity within the NIH. There is an NIH Obesity Research Task Force, which issued a report in 2011, affirmed in 2019, outlining challenges and opportunities in guiding obesity research. Given the complexity of obesity as a disease and the prevalence across the population when compared to other conditions, this response seems grievously inadequate.A core feature of the obesity disease process is chronic inflammation. Among other chemokines, adipocytes secrete interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α, which promote chronic inflammation and metabolic dysfunction. With the expansion of adipose tissue, immune cells infiltrate the fat and further mediate the inflammatory process. Why some patients experience poor outcomes of obesity while others seem to be protected is poorly understood. With the onset of the 2009 influenza H1N1 pandemic, obesity gained national attention as a major co-factor of severe disease and mortality.8Webb S.A. Pettila V. Seppelt I. Bellomo R. Bailey M. et al.ANZIC Influenza Investigators. Critical care services and 2009 H1N1 influenza in Australia and New Zealand.,9Morgan O.W. Bramley A. Fowlkes A. Freedman D.S. Taylor T.H. Gargiullo P. et al.Morbid obesity as a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1) disease. These observations spawned further study of the dysregulated response to not only influenza infection but also influenza vaccine in patients with obesity.10Paich H.A. Sheridan P.A. Handy J. Karlsson E.A. Schultz-Cherry S. Hudgens M.G. et al.Overweight and obese adult humans have a defective cellular immune response to pandemic H1N1 influenza A virus., 11Honce R. Karlsson E.A. Wohlgemuth N. Estrada L.D. Meliopoulos V.A. Yao J. et al.Obesity-related microenvironment promotes emergence of virulent influenza virus strains., 12Sheridan P.A. Paich H.A. Handy J. Karlsson E.A. Hudgens M.G. Sammon A.B. et al.Obesity is associated with impaired immune response to influenza vaccination in humans. These phenomena were replicated with the onset of the coronavirus disease 2019 (COVID-19) pandemic, with similarly high rates of hospitalization and death in patients with obesity.13Goyal P. Choi J.J. Pinheiro L.C. Schenck E.J. Chen R. Jabri A. et al.Clinical characteristics of Covid-19 in New York City., 14Goyal P. Ringel J.B. Rajan M. Choi J.J. Pinheiro L.C. Li H.A. et al.Obesity and COVID-19 in New York City: a retrospective cohort study., 15Lighter J. Phillips M. Hochman S. Sterling S. Johnson D. Francois F. et al.Obesity in patients younger than 60 years is a risk factor for COVID-19 hospital admission., 16Otto W.R. Geoghegan S. Posch L.C. Bell L.M. Coffin S.E. Sammons J.S. et al.The epidemiology of severe acute respiratory syndrome coronavirus 2 in a pediatric healthcare network in the United States., 17Foster C.E. Marquez L. Davis A.L. Tocco E. Koy T.H. Dunn J. et al.A surge in pediatric coronavirus disease 2019 cases: the experience of Texas Children's Hospital from March to June 2020. In my practice, virtually all of the children with severe COVID-19 symptoms and hospital admission were adolescents with severe obesity. Similar to the blunted response to influenza vaccine, the findings from an early study suggested that patients with central adiposity who received a COVID-19 mRNA vaccine had a neutralizing antibody level lower than that in patients without central adiposity.18Watanabe M. Balena A. Tuccinardi D. Tozzi R. Risi R. Masi D. et al.Central obesity, smoking habit, and hypertension are associated with lower antibody titres in response to COVID-19 mRNA vaccine. The findings from that immunogenicity study need to be duplicated in larger-scale, population-wide studies, but they raise a concern that patients with obesity may need additional measures for COVID-19 prevention.The experts who contributed to this issue make the point that more options for the treatment of obesity are available than ever before. Six medications have been approved by the US Food and Drug Administration, and a variety of surgical options facilitate weight loss. However, the medications are viewed by insurance payors as "lifestyle medications," similar to agents used for treating nicotine addiction or hair loss, and as a result their costs are not covered by most health insurance plans.19Newly Approved Obesity Drug Wegovy Holds Promise, But Faces Reimbursement Challenges. A study authored by Dr. Fatima Stanford, one of the experts contributing to this issue, demonstrated that most public insurance plans in the United States offer no coverage at all for the costs of anti-obesity medications.20US health policy and prescription drug coverage of FDA-approved medications for the treatment of obesity. The ones that cover medication costs do so only for patients who pay the highest premiums, or they cover the costs of the medications that appear to be least effective. This lack of coverage extends to diet counseling for patients and their families, which costs a fraction of the costs of medical and surgical treatment options. In a modeling study in Medicare recipients, a combination of cognitive–behavioral therapy and medication was cost-saving over a 10-year period.21Chen F. Su W. Ramasamy A. Zvenyach T. Kahan S. Kyle T. et al.Ten-year Medicare budget impact of increased coverage for anti-obesity intervention. As the US health care system slowly transitions to a value-based payment model, it is hoped that these coverage trends will improve.Given the prevalences of obesity and severe obesity, clinicians need to carefully consider how to dose medications in patients with obesity. The presence of obesity in any adult or child can dramatically change drug metabolism, and the dose recommended for nonobese adults may be insufficient for treating diseases in patients with obesity.22Brill M.J. Diepstraten J. van Rongen A. van Kralingen S. van den Anker J.N. Knibbe C.A. Impact of obesity on drug metabolism and elimination in adults and children. While the earlier-mentioned mortality rate in patients with severe infection may be entirely attributable to obesity-related immune dysregulation, it is worth considering that suboptimal dosing of medications needed for supportive care may also play a role. We at Clinical Therapeutics are proud to be a forum for publishing research on this topic. A search of the term obesity on our website yielded 770 articles, and we have organized several prior Topic Updates on various aspects of obesity that are freely available to all (https://www.clinicaltherapeutics.com/content/specialfocus). We continue to welcome studies that advance our understanding of how to best treat patients with obesity.

We sincerely thank the experts who contributed to this Update. Their continued advocacy of their patients should be an example for all of us. We hope that the articles encourage you as clinicians and researchers to reflect on ways to help advance the care of patients with obesity. The first steps may be to look in the mirror and determine whether you harbor the most common biases and assumptions about patients with obesity, and then to make changes to counter those biases.

Acknowledgments

I thank Dr. Caren Mangarelli for her input on the style and content of this editorial.

Appendix. Supplementary materialsReferences

Centers for Disease Control and Prevention (CDC). Adult Obesity Facts [CDC website]. Updated February 11, 2021. Available at: https://www.cdc.gov/obesity/data/adult. June 1, 2021.

US Census Bureau. Quick Facts—United States 2021 [US Census Bureau website]. Available at: https://www.census.gov/quickfacts/fact/table. June 1, 2021.

Centers for Disease Control and Prevention (CDC). Heart Disease Facts [CDC website]. Updated September 8, 2020. Available at: https://www.cdc.gov/heartdisease/facts. June 1, 2021.

Centers for Disease Control and Prevention (CDC). United States Cancer Statistics: Data Visualizations [CDC website]. 2021. Available at: https://gis.cdc.gov/Cancer/USCS/DataViz. June 1, 2021.

National Institutes of Health (NIH)

Estimates of Funding for Various Research, Condition, and Disease Categories.

()

National Institutes of Health, Obesity Research Task Force. NIH-Supported Obesity Research [NIH website]. 2021. Available at: https://www.obesityresearch.nih.gov. June 1, 2021.

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Overweight and obese adult humans have a defective cellular immune response to pandemic H1N1 influenza A virus.

Obesity (Silver Spring). 21: 2377-2386Honce R. Karlsson E.A. Wohlgemuth N. Estrada L.D. Meliopoulos V.A. Yao J. et al.

Obesity-related microenvironment promotes emergence of virulent influenza virus strains.

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Obesity is associated with impaired immune response to influenza vaccination in humans.

Int J Obes (Lond). 36: 1072-1077Goyal P. Choi J.J. Pinheiro L.C. Schenck E.J. Chen R. Jabri A. et al.

Clinical characteristics of Covid-19 in New York City.

N Engl J Med. 382: 2372-2374Goyal P. Ringel J.B. Rajan M. Choi J.J. Pinheiro L.C. Li H.A. et al.

Obesity and COVID-19 in New York City: a retrospective cohort study.

Ann Intern Med. 173: 855-858Lighter J. Phillips M. Hochman S. Sterling S. Johnson D. Francois F. et al.

Obesity in patients younger than 60 years is a risk factor for COVID-19 hospital admission.

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J Pediatric Infect Dis Soc. 9: 523-529Foster C.E. Marquez L. Davis A.L. Tocco E. Koy T.H. Dunn J. et al.

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J Pediatric Infect Dis Soc. 10: 593-598Watanabe M. Balena A. Tuccinardi D. Tozzi R. Risi R. Masi D. et al.

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Diabetes Metab Res Rev. ()

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() ()

US health policy and prescription drug coverage of FDA-approved medications for the treatment of obesity.

Int J Obes (Lond). 42: 495-500Chen F. Su W. Ramasamy A. Zvenyach T. Kahan S. Kyle T. et al.

Ten-year Medicare budget impact of increased coverage for anti-obesity intervention.

J Med Econ. 22: 1096-1104Brill M.J. Diepstraten J. van Rongen A. van Kralingen S. van den Anker J.N. Knibbe C.A.

Impact of obesity on drug metabolism and elimination in adults and children.

Clin Pharmacokinet. 51: 277-304Article InfoPublication History

Published online: June 27, 2021

Accepted: June 7, 2021

Publication stageIn Press Corrected ProofIdentification

DOI: https://doi.org/10.1016/j.clinthera.2021.06.003

Copyright

© 2021 Elsevier Inc.

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