2024/11/27 by Dimitri J. Pournaras, Ildiko Lingvay, Priya Sumithran · 1 voice
Medicine · #Pharmacology and Obesity Treatment #Bariatric Surgery and Outcomes #Diet and metabolism studies
paper · doi:10.1093/bjs/znae294
openalex publication_date 2024/11/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
As evidence for the efficacy and safety of the new generation of obesity medications accumulates, it is timely to reconsider the approach to obesity treatment. Although bariatric surgery remains the most effective and durable intervention, new medications are rapidly gaining popularity because they are perceived as a more approachable and reversible option. Long-term studies comparing the effectiveness, safety, and cost-effectiveness of bariatric surgery with those of new antiobesity medications are lacking, and would be informative. However, rather than viewing these highly effective and complementary treatment approaches as inevitable competitors, learning in whom, when, and how to combine them could be even more valuable and relevant to patient care. Obesity is a highly stigmatized chronic, relapsing disease. To treat it optimally, lessons from other chronic conditions could be adopted. As in cancer care, combining obesity treatment modalities such as pharmacotherapy, endoscopic therapies, use of devices, and bariatric surgery may well be the way forward, either before surgery (neoadjuvant) or after operation (adjuvant or rescue)1. How to accomplish this is underinvestigated, as highlighted by the systematic review2 of the available evidence demonstrating the research gaps and paucity of high-quality RCTs. Resolving this will require evidence to fill the gaps in understanding of the fundamental principles of obesity care that have been exposed by the emergence of more effective treatment approaches. One such example is: what is the appropriate treatment target? Is it loss of a certain percentage of bodyweight (say 15%)—a relative number linked to an arbitrary (and variable) starting point?3 Is it reversal of obesity-associated health and functional impairments? But would that be enough to prevent their subsequent progression? Is it a bodyweight (BMI) or anthropometric measure of adiposity within the range deemed ‘normal’ or ‘low risk’? But how would this risk be defined, given that estimates of population-level risk are not suitable for individuals? An international consensus4 by a multidisciplinary team of experts in obesity management has provided some useful and authoritative recommendations, and a practical blueprint for obesity care to temporarily navigate this uncertainty. However, it is clear that high-quality research is imperative to inform evidence-based care. Clinical trials to establish the long-term safety, efficacy, and cost-effectiveness of multimodal strategies are urgently needed, as well as studies that inform optimal patient selection for different treatment approaches. Perhaps the recent successes in this field are also the biggest challenge. The growing number of promising therapies currently under investigation adds another layer of complexity in designing long-term studies that will remain relevant by the time they are completed. Although the challenges remain numerous, so do the opportunities, so we should not be deterred from tackling the right clinical questions. We are at a seminal time in obesity care. To paraphrase Sir Winston Churchill: this is not the end. Not even the beginning of the end. But perhaps this is the end of the beginning. The future looks very bright, but we need the right studies to inform our approach and best treatment algorithms to optimize the care of people whose health is impaired by this highly prevalent disease. The authors have no funding to declare. Dimitri Pournaras (Conceptualization, Writing—original draft, Writing—review & editing), Ildiko Lingvay (Conceptualization, Writing—original draft, Writing—review & editing), and Priya Sumithran (Conceptualization, Writing—original draft, Writing—review & editing) D.J.P. has been funded by the Royal College of Surgeons of England. He receives consulting fees from Johnson & Johnson, GSK, Novo Nordisk and Pfizer and payments for lectures, presentations, and educational events from Johnson & Johnson, Medtronic, Novo Nordisk and Sandoz. I.L. received research funding (paid to institution) and/or product from Novo Nordisk, Sanofi, Boehringer-Ingelheim, Dexcom. I.L. received research related consulting fees (paid to institution) from Novo Nordisk. I.L. received advisory/consulting fees and/or other support from: Abbvie, Altimmune, Alveus Therapeutics, Astra Zeneca, Bayer, Betagenon AB, Bioio Inc., Biomea, Boehringer-Ingelheim, Carmot, Cytoki Pharma, Eli Lilly, Intercept, Janssen/J&J, Juvena, Keros Therapeutic, Inc, Mediflix, Merck, Metsera, Neurocrine, Novo Nordisk, Pharmaventures, Pfizer, Regeneron, Sanofi, Shionogi, Structure Therapeutics, TARGET RWE, TERNS Pharma, The Comm Group, WebMD, and Zealand Pharma. P.S. reports co-authorship of manuscripts with medical writing assistance from Novo Nordisk and Eli Lilly.