Journal of Obesity & Metabolic Syndrome

Search

Article

J Obes Metab Syndr 2023; 32(4): 285-288

Published online December 30, 2023 https://doi.org/10.7570/jomes23078

Copyright © Korean Society for the Study of Obesity.

The Transformative Impact of New Anti-Obesity Medications: A Paradigm Shift in Medical Practice?

Arya M. Sharma *

Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada

Correspondence to:
Arya M. Sharma
https://orcid.org/0000-0001-9360-6519
Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine and Dentistry, University of Alberta, 13-103 Clinical Sciences Building, 11350-83 Avenue NW, Edmonton, AB T6G 2G3, Canada
Tel: +1-780-248-1861
E-mail: amsharm@ualberta.ca

Received: November 24, 2023; Reviewed : December 12, 2023; Accepted: December 12, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Obesity, once considered a personal problem, it is now widely recognised as a highly prevalent, complex, progressive, and relapsing chronic disease, characterized by abnormal or excessive body fat (adiposity), that impairs health.1 As for most chronic diseases, “lifestyle management” and behaviour changes remain a key principle of obesity management; however, this approach is unsuccessful in the long-term with the majority of patients regaining most of the lost weight (and sometimes more). This is in stark contrast to patients undergoing bariatric/metabolic surgery, who are generally able to sustain 20% to 30% weight loss in the long-term, with important health benefits.2 Surgery, although considered safe and effective, has inherent risks and is limited in its scalability to address the millions battling excess weight.

Recent breakthroughs in anti-obesity medications (AOMs) allow specific targeting of the homeostatic and hedonic centres of appetite regulation that hinder long-term weight loss. In simple terms, AOMs counteract the appetitive counter response to negative energy balance that serves to limit the degree of weight loss and promote weight regain. As outlined in the recent article by Jeon et al.3 on the obesity pharmacotherapy guidelines recommended by the Korean Society for the Study of Obesity (KSSO), pharmacotherapy is strongly recommended by the KSSO for Korean adults with a body mass index of 25 kg/m2 or higher who have not achieved weight loss through non-pharmacological treatments. This recommendation is in line with the recommendations by other national organisations like Obesity Canada, which considers AOMs an essential approach to achieving and sustaining healthier eating behaviours.1

Despite these recommendations, access to the novel generation of nutrient-stimulated hormone (NuSH) based AOMs (e.g., semaglutide, tirzepatide) remains challenging. Although these medications are now approved for obesity management (in the United States) and offer the promise of double digit weight loss, they are generally not reimbursed by insurance. Moreover, supply has failed to keep up with the exceedingly high demand for these medications. Whether increasing evidence for reduction in obesity associated comorbidities (e.g., diabetes, hypertension) or the recent demonstration of a 20% reduction in cardiovascular endpoints for semaglutide 2.4 mg in the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT)4 will lead to better access, at least for high-risk individuals, remains to be seen.

There is little doubt that these new AOMs as well as those currently in various stages of development3 have the potential to change medical practice. As outlined in a recent commentary, I have suggested that AOMs should be accepted as first-line medical treatment for any condition that is causally related to excess body weight.5 These conditions include a large number of common medical issues including newly diagnosed type 2 diabetes mellitus, obesity-related hypertension, metabolic (dysfunction)-associated fatty liver disease, or obstructive sleep apnoea. Furthermore, AOMs may also play an important role in the many medical conditions, which, although not causally related to excess body fat, may be aggravated or complicated by its presence. This approach may eventually lead to AOMs as the most widely prescribed medication for chronic disease in all of medical practice.

However, for this paradigm shift to take place, several things need to happen. First, we need long-term studies of these medications specifically aimed at demonstrating benefits for distinct health outcomes rather than simply weight loss alone. Second, the use of AOMs as an approach to managing obesity-related comorbidities and complications must be addressed in clinical practice guidelines that address these conditions. Third, access to these medications has to be vastly improved with lower cost, reimbursement and production capacities to meet the potential demand. This will be essential to ensure cost-effectiveness, as balancing efficacy with affordability will remain a challenge for any healthcare system. As costs decrease and evidence for effectiveness increases, more positive assessments of cost-effectiveness will emerge, and advocacy for insurance coverage will remain critical in ensuring equitable access to AOMs.

One important caveat to reaping the benefits of these medications will be to ensure that patients adhere to use as prescribed. As outlined in the Fig. 1, the critical phase in obesity management is the maintenance of weight loss, during which discontinuation of treatment generally results in weigh regain. However, as with all medications for chronic disease, it is likely that many patients with obesity will not initiate or will discontinue prescribed medical treatments for a variety of reasons. As described in a recent Organisation for Economic Co-operation and Development (OECD) Report,6 approximately half of the population that receives prescriptions show poor adherence, leading to severe health complications, premature deaths and an increased use of healthcare services. Patients with chronic diseases are particularly vulnerable to poor health outcomes if they do not adhere to their medications. Mortality rates for patients with diabetes and heart disease who do not adhere to medication are nearly twice as high as for those who do adhere. In fact, the three most prevalent chronic conditions—diabetes, hypertension and hyperlipidaemia—are the diseases with the highest avoidable costs, for which every extra United States dollar (USD) spent on medications for patients who do adhere can generate between USD 3 to 13 in savings on avoidable emergency department visits and inpatient hospitalisations alone.6 Overall, the data show that among patients with diabetes, hypertension and hyperlipidaemia, up to 30% never fill their first prescription; of those who do fill their first prescription, only 50% to 70% take their medications regularly (i.e., at least 80% of the time) and less than 50% of these patients still take their medications within 2 years of initial prescription.6

The OECD Working Paper6 identifies three key drivers of non-adherence.

(1) Firstly, poor awareness among all stakeholders. The problem of poor adherence to medication has generally been overlooked and rarely explicitly included in national health policy agendas. Consequently, few OECD countries routinely measure rates of adherence to medication. Even fewer use those measurements to systematically incentivise improvements in adherence and health outcomes. Health professionals—physicians, nurses, and pharmacists—underestimate the incidence of the problem in their patients. There is a dearth of evidence on cost effective interventions that improve adherence at a system level.

(2) Secondly, wrong targets for interventions and poor incentives. Discussions of non-adherence tend to attribute the problem exclusively to the individual patient, while the evidence suggests that health system characteristics—in particular the quality of patient-provider interaction, cumbersome procedures for refilling prescriptions, or out-of-pocket costs of medications—are lead drivers. Most interventions tackling poor adherence have focused on patients, particularly their forgetfulness and incorrect beliefs about medications, rather than taking a systems level approach by understanding and changing the context in which healthcare is provided.

(3) Thirdly, lack of patient involvement. Patients with chronic conditions frequently feel that the decision about their therapy did not involve them and are inclined to rebuff it or lack motivation to follow the therapy consistently. From a patient perspective, a chronic condition poses not only health problems but also long-term personal and social challenges. Yet, the current disease focused, as opposed to person-centred approach to healthcare delivery leaves little or no room for consideration of the personal aspects of a patient’s condition.

All these barriers will clearly also apply to obesity management. The high cost of AOMs exacerbates non-adherence, and their effects can only be realised if the appropriate patients use them as prescribed. Unfortunately, many patients, providers and payers do not consider obesity a chronic disease requiring long-term treatment. Thus, patients may be looking at medications as a short-term fix to quickly lose weight, providers may stop medications once weight loss targets are achieved and payers may limit reimbursements for AOMs to a given time period (e.g., 12 to 24 months) rather than considering them for indefinite long-term use (as is standard practice for medications for other chronic diseases).

Currently, health systems generally do not support chronic disease management approaches to obesity management or focus on issues of long-term adherence to AOMs. Without such focus, which includes fair and equitable reimbursements for such treatments without instating additional barriers (e.g., cumbersome prior-authorisation forms, significant co-pays, time-limited approval), patient use of these medications will likely remain severely limited.

Finally, as discussed in the Canadian Obesity Clinical Practice Guidelines, patient-centric care with shared decision making will be essential to ensure that patients understand and support the need for long-term management of obesity.1 In obesity, stigma, including that of using medications to control weight, and internalised weight bias may pose an additional significant barrier to the broad and long-term use of these medications.7

In conclusion, in the era of highly effective AOMs, significant challenges remain to be resolved before the millions living with this chronic disease can reap the benefits. Not only must clinicians prescribe medications responsibly with due consideration to limiting prescriptions to eligible patients with attention to potential risks and benefits, consideration must also be given to individualization, ongoing monitoring and focus on health outcomes rather than weight alone.

Arya M. Sharma has received honoraria as an independent medical, research and/or educational consultant from Aidhere, Allurion, Boehringer Ingelheim, Currax, Eli-Lilly, Johnson & Johnson, Medscape, MDBriefcase, Novo Nordisk, Oviva, and Xenobiosciences.

Fig. 1. Obesity management can be conceptualised as three distinct phases. Phase I, weight stabilisation or prevention of further weight gain; Phase II, weight loss; Phase III, weight loss maintenance and prevention of weight regain.
  1. Wharton S, Lau DC, Vallis M, Sharma AM, Biertho L, Campbell-Scherer D, et al. Obesity in adults: a clinical practice guideline. CMAJ 2020;192:E875-91.
    Pubmed KoreaMed CrossRef
  2. Carlsson LM, Sjöholm K, Jacobson P, Andersson-Assarsson JC, Svensson PA, Taube M, et al. Life expectancy after bariatric surgery in the Swedish obese subjects study. N Engl J Med 2020;383:1535-43.
    Pubmed KoreaMed CrossRef
  3. Jeon E, Lee KY, Kim KK. Approved anti-obesity medications in 2022 KSSO guidelines and the promise of phase 3 clinical trials: anti-obesity drugs in the sky and on the horizon. J Obes Metab Syndr 2023;32:106-20.
    Pubmed KoreaMed CrossRef
  4. Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med 2023;389:2221-32.
    Pubmed CrossRef
  5. Sharma AM. Does this person have obesity? EClinicalMedicine 2023;58:101935.
    Pubmed KoreaMed CrossRef
  6. Khan R, Socha-Dietrich K. OECD Health Working Paper No. 105. Investing in medication adherence improves health outcomes and health system efficiency: adherence to medicines for diabetes, hypertension, and hyperlipidaemia [Internet]. Organisation for Economic Co-operation and Development; 2018 [cited 2023 Dec 20]. Available from: https://one.oecd.org/document/DELSA/HEA/WD/HWP(2018)2/En/pdf.
  7. Nutter S, Eggerichs LA, Nagpal TS, Ramos Salas X, Chin Chea C, Saiful S, et al. Changing the global obesity narrative to recognize and reduce weight stigma: a position statement from the World Obesity Federation. Obes Rev 2024;25:e13642.
    Pubmed CrossRef