Medications and Obesity: Exploring the Landscape and Advancing Comprehensive Care: Proceedings of a Workshop (2024)

___________________

¹ This list is the rapporteur’s summary of points made by the individual speakers identified, and the statements have not been endorsed or verified by the National Academies of Sciences, Engineering, and Medicine. They are not intended to reflect a consensus among workshop participants.

The third session of the workshop featured presentations and a discussion about obesity CPGs for adult and pediatric populations, with a focus on CPG development and research gaps that influence content. It also explored considerations regarding AOMs, subpopulations, and lifestyle interventions. David E. Arterburn, Kaiser Permanente Washington Health Research Institute, and Anand K. Parekh, Bipartisan Policy Center, moderated the session.

ADULT CLINICAL PRACTICE GUIDELINES (CPGs)

Jamy D. Ard, Wake Forest University School of Medicine, outlined the history of North American CPGs for obesity treatment in adults and discussed considerations regarding their purpose and limitations. He explained that CPGs are a function of the questions asked, evidence available, resources dedicated, and people writing them. Moreover, CPGs may be shaped by the perspectives and agendas of their authors. Although CPGs can be used to improve care, some parties use them to allocate, limit, or even hinder care, Ard cautioned. Furthermore, given the rate of scientific advances and the length of time required to develop a CPG, it may already be out of date by the time it is published. Therefore, Ard suggested treating CPGs as living documents that are adapted and refined—particularly for CPGs related to obesity treatment, a field that has seen rapid and substantial changes in recent years.

the NIH panel convened in 1995–1998, patient presentation of excess body weight concerns was predominantly composed of initial complaints, with few patients demonstrating lifelong experience of obesity. Ard asserted that in this context, a rubric that considered weight gain, risk factors, and patient interest in losing weight and introduced patients to low-risk interventions with a reasonable probability of success was an appropriate tool. The panel developed a 10-step practical guide for PCPs that outlined how to measure BMI and assess patient motivation. It recommended a basic balance-deficit diet with modest calorie reduction, an increase in physical activity, and ongoing monitoring. Ard stated that more than 2 decades later, PCPs continue to use the recommendations in this guidance.

Updated Obesity CPG (2013)

From 1998 to 2008, the U.S. prevalence of obesity continued to increase sharply, said Ard (CDC, 2008). By 2008, a majority of states had

25–29 percent of adults with BMIs ≥30, with the rates in some states exceeding 30 percent. Once again, NIH and NHLBI convened an expert panel, this time to update the CPG. Ard was a member of this panel, and he recalled that during this process, the Institute of Medicine produced a report that declared that systematic evidence review and CPG development should be separate activities. In response, NIH determined to focus on these reviews and cease developing CPGs, ceding that responsibility to professional societies. This shift extended the process of updating the obesity CPG to a 5-year timeline. In 2013, the American Heart Association, American College of Cardiology, and the Obesity Society (TOS) released guidelines for managing overweight and obesity in adults (Jensen et al., 2014) and NHLBI published a systematic evidence review of studies 1998–2009 (NHLBI, 2013). Some major obesity studies, such as Look AHEAD, were published during the panel timeline extension. Therefore, the evidence review also included major studies published in 2011 and 2012. The 2013 CPG addressed the expected health benefits of weight loss, health risks associated with overweight and obesity, effectiveness of various dietary strategies and a comprehensive lifestyle approach for weight loss and maintenance, and efficacy and safety of bariatric surgery. It also established cut points for overweight and obesity related to waist circumference and BMI. Ard noted that in the early 2000s, controversy existed around whether low-fat or low-carbohydrate diets were more effective, and the CPG addressed this.

Limitations and Clinical Implications of the 2013 CPG

The 2013 CPG received immediate criticism upon publishing due to the lack of focus on pharmacotherapy, said Ard. He explained that at that time, AOMs were in flux. Rimonabant and sibutramine were withdrawn in 2007 and 2010, respectively. Lorcaserin and extended-release phentermine/topiramate were approved in 2012, just as the panel was completing the CPG. Ard commented that changing the project approach and timeline midway through the process generated a lack of direction and a gap in the literature review, given that it featured a comprehensive review of studies published 1998–2009 but only included major studies after that. Ard said that in retrospect, these challenges created some problematic issues in the final product.

The prevalence of obesity continued to increase, and by 2013, all states had 20 percent or more of the adult population with BMIs ≥30, Ard noted. In Mississippi and West Virginia, the rates exceeded 35 percent. After the updated CPG was published in 2013, clinical implications surfaced. Payers made determinations about treatment coverage based on the CPG, and the absence of pharmacology influenced coverage of AOMs coming to the market. Similarly, some policy makers interpreted the lack of CPG discussion of AOMs as an indication of low importance. Some clinicians overlooked recent evidence on the effectiveness of AOMs and based their practices on

the older evidence included in the literature review or established patterns carried forward. Furthermore, a shift from open to laparoscopic bariatric surgery was increasing its safety, but the CPG did not reflect this changing dynamic, added Ard.

Additional Obesity CPGs

To address the gaps in the 2013 CPG, other groups and professional societies began issuing their own guidelines, Ard stated. For instance, the Endocrine Society (Apovian et al., 2015) and American Gastroenterological Association (Grunvald et al., 2022) released CPGs on pharmacological interventions for adults with obesity. The American Association of Clinical Endocrinologists and American College of Endocrinology put forward an obesity CPG focused on medical care that includes treatment algorithms indicating when pharmacotherapy and other interventions are appropriate (Garvey et al., 2016). Ard pointed out that as the number of obesity CPGs has grown, so too has confusion as to which one should become the basis for payment and reimbursement considerations. Furthermore, some CPGs are intended to shift practice. In 2022, the American Society for Metabolic and Bariatric Surgery and International Federation for the Surgery of Obesity and Metabolic Disorders issued a CPG that recommended the indication for bariatric surgery be reduced from the BMI of 40 established by the 1991 consensus statement to a BMI of 35–39.9 without a requirement of obesity complications, said Ard.

International groups have also developed CPGs for obesity. Ard described the CPG created by the Canadian Medical Association and Obesity Canada as the most comprehensive CPG available for adults (Wharton et al., 2020). He noted that it emphasizes including the patient voice, is based on a large literature review, and provides 80 recommendations on a wide range of clinical and scientific issues that were developed via consensus building. Several smaller countries lacking the infrastructure to develop their own CPGs have adopted or adapted Canada’s guidelines. Canada treats the CPG as a living document by updating it regularly, incorporating new data as they become available, he noted. Numerous organizations within the obesity space and from a broad international grouping have endorsed it. Ard said that developing a similar guideline would be an expensive venture and might generate only incremental benefit.

Considerations Related to CPGs

Ard commented that even the most comprehensive guidelines will be limited by the availability of high-quality evidence. The professionals developing them determine the topics considered for inclusion. Without a

guideline, clinical decision making is informed by best practice standards, he added, noting that this is particularly true in obesity medicine, where non-science-based therapies abound in both the commercial and clinical spaces and evidence on comparative effectiveness is limited. For instance, data are available from phase 3 trials that compare an active drug to a placebo, but studies comparing active drugs to one another and in particular patient populations are lacking. TOS and an international group of obesity-related professional societies are working to create standards of care to fill this gap. Ard emphasized that when multiple CPGs are available, it becomes uncertain which ones will inform decisions about reimbursement, coverage of care, and indications for treatment. He explained that this issue becomes more complex when considering international guidelines, as U.S. policy makers and payers may be reluctant to rely on a CPG from another country even if it carries the endorsement of numerous relevant U.S. professional societies.

PEDIATRIC CPGs FOR ANTI-OBESITY MEDICATIONS

Sarah E. Barlow, University of Texas Southwestern Medical Center, reviewed the current CPGs around AOMs for pediatric populations. U.S. obesity in children has paralleled that seen in adults, she noted. From the mid-1960s until 1980, the prevalence was approximately 5 percent (Fryar et al., 2020). Over the past 4 decades, rates have risen steadily across age groups and average 18.5 percent for all ages and 20.6 percent for those aged 12–19 (Ogden et al., 2015). This disproportionally affects Black and Hispanic children (Ogden et al., 2015). Furthermore, severe obesity is not uncommon among children. She explained that the change in linear height in children requires using BMI percentiles and other units that index BMI to norms for age and sex. These metrics are used to define class 2 or “severe” obesity (comparable to a BMI score of 35 kg/m² in adults) and class 3 or “very severe” obesity (comparable to a BMI score of 40 kg/m² in adults). In 2016, over 5 percent of girls and almost 7 percent of boys had BMIs in class 2, and approximately 2 percent of both sexes had BMIs in class 3 (Skinner et al., 2018). Data from 2020 indicate that almost 13 million children, or 20 percent, have obesity and over 3 million children, or 5 percent, have severe obesity. Barlow emphasized that these statistics reflect substantial numbers of children with health issues that should be addressed before adulthood.

Development of the AAP CPG (2023)

In 2023, the AAP released a CPG for the evaluation and treatment of children and adolescents with obesity, said Barlow. She noted that expert committee recommendations had been published in 2007, when

randomized, rigorous studies were too limited to enable developing a guideline. She explained that the 2023 AAP CPG was informed by a literature review with a scope beginning in the 1950s that focused on the risk of comorbidities and clinic-based, effective treatments. It incorporated findings from 16,000 abstracts, 1,600 full articles, and 400 studies into two technical reports. The writing groups carefully examined these technical reports, assessed the evidence based on quality, benefit, and harm, and developed 13 key action statements designed to communicate clear directives to providers (Hampl et al., 2023). When the evidence was not adequate, they drafted additional consensus statements, Barlow added.

The CPG key action statements use modal verbs to convey the associated obligation level, Barlow explained, with “must” conveying the highest obligation level, “should” reflecting an intermediate level, and “may” communicating the lowest obligation level (IOM, 2011; Rosenfield et al., 2013). She clarified that although some people interpret “should” to mean “must,” these terms convey different obligation levels in the context of the AAP CPG. Barlow highlighted Key Action Statement 9, which provides an overview of obesity treatment designed to remind pediatric health care providers (PHCPs) of the chronic and complex nature of obesity:

Additional information accompanying this key action statement emphasizes that physicians should consider various contextual factors and maintain support for both the child and family over time and that treatment intensity and support should vary in response to the relapsing and remitting nature of obesity as a chronic disease. Barlow underscored that in pediatrics, interventions address not only the patient but also the patient’s family.

Health Behavior and Lifestyle

Key Action Statement 11 in the AAP CPG states that PHCPs should provide or refer children 6+ years with overweight and obesity to IHBLT, said Barlow, noting that this is based on grade B, or fairly strong, evidence. It also says that PHCPs may provide or refer children aged 2–5 to IHBLT, based on grade C evidence due to less literature available in this area. The key action statement specifies that IHBLT is more effective with greater contact hours, with the most effective involving at least 26 hours

of in-person, family-based, multicomponent treatment over 3–12 months. Barlow pointed to a U.S. Preventive Services Task Force (2017) study that found that programs featuring less than 25 hours demonstrate a low likelihood of significant effect, and only programs offering 26 or more hours showed a consistent, significant difference between the intervention and control groups. The components of IHBLT include eating and nutrition to establish healthy, sustainable dietary patterns; physical activity; behavior change strategies; and family engagement. She clarified that these interventions do not recommend a particular diet or macronutrient balance, nor do they feature calorie restriction as a goal; rather, they work with families to move toward a healthy, balanced diet. Emphasizing the family engagement aspect, IHBLT interventions are directed at the entire family and not solely the child. Barlow stated that implementation is variable—involving individual, group, or combination treatment—without a decrease in effect. Furthermore, implementation can take place in a health care setting or in a community setting linked to health care, and it can be in person or virtual. Studies conducted during the COVID-19 pandemic afforded data on virtual implementation, said Barlow.

The CPG reviewed the effects of IHBLT and found modest changes in BMI measures, which Barlow explained is a complicated metric for children given linear growth in this population (Hampl et al., 2023). Furthermore, these interventions demonstrate improvement in cardiovascular risk factors, such as blood pressure, insulin, glucose, obstructive sleep apnea, and nonalcoholic fatty liver disease. Limited data indicate no worsening of mental health from IHBLT, although Barlow noted that youth with serious mental health disorders are oftentimes excluded from studies. Given that some children with mental health disorders also have obesity and need treatment, this area warrants additional research, she said. Underscoring a concerning risk of ED among people with obesity, Barlow spotlighted that limited studies indicate that high-quality IHBLT may reduce disordered eating, although more research is needed.

Pharmacotherapy

The AAP CPG’s Key Action Statement 12 states that “Pediatric health care providers should offer adolescents 12 years and older with obesity (BMI ≥95th percentile) weight-loss pharmacotherapy, according to medication indications, risks, and benefits, as an adjunct to health behavior and lifestyle treatment.” Barlow underscored that the CPG states that pharmacotherapy should be offered, but not necessarily prescribed, and emphasizes the importance of IHBLT. Recently approved by FDA for use in adolescents, three AOMs have been found to be effective in people aged 12–17. Liraglutide, a daily GLP-1, was approved in December 2020 based on a 56-week

double-blind RCT that showed a decrease of approximately 4.3 percent BMI (Kelly et al., 2020). Barlow said that BMI is a reasonable metric to use with adolescents, given that many of them have completed their linear growth. In a similar study, phentermine/topiramate, an AOM approved for adolescents in 2022, demonstrated a 5 percent decrease in BMI at a medium dose and 7 percent at the highest dose (Kelly et al., 2022). Semaglutide, a weekly GLP-1 agonist, was approved for adolescents in 2023 and showed a substantial decrease of 16 percent BMI over 56 weeks, Barlow highlighted (Weghuber et al., 2022).

The benefits and harms of pharmaceutical treatment are similar to those in adults but with some specific concerns, said Barlow. Benefits include reduced adiposity and improved current and future metabolic health. The desired outcomes with AOMs include improved quality and quantity of nutritional intake, physical activity, quality of life, and mental health. Potential risks include loss of muscle mass, which has not been well studied and is important in children, she said. Weight loss can limit linear growth and be excessive or too rapid. Barlow highlighted that decreased bone mass and bone mineral density when bone is being built warrants careful provider attention. Mental and emotional health concerns include uncovering or worsening disordered eating and a lack of improvement or decrease in quality of life. Inequitable access to AOM treatment is also a concern, Barlow added.

Pediatric Obesity Treatment Barriers

Although the CPG recommends treatment for obesity, barriers prevent many patients from receiving it. Barlow noted that IHBLT has a measurable effect on obesity, but individual office visits in a health care setting are not conducive to family engagement. She described that more practical implementation would involve delivery in a community setting closer to where families reside that affords adequate space for an entire family to attend and engage in physical activity. Furthermore, sessions could be provided by health educators or other nonphysicians outside of typical school and work hours. However, insurance coverage does not extend to community settings. Moreover, the CPG recommends AOM treatment as an adjunct to IHBLT, but insurance often does not cover AOMs. Barlow explained that commercial plans often exclude AOMs from benefits in response to employer requests. Similarly, Medicaid and the Children’s Health Insurance Program (CHIP) exclude AOMs in many states. Additionally, national AOM shortages limit access, as do the implementation challenges that primary care pediatricians and families face in using injectable medications, said Barlow.

These and other barriers create a discrepancy between children who would benefit from obesity treatment and those who receive it, Barlow stated. Factors contributing to access inequity include lack of insurance coverage; challenges in the treatment path, particularly for IHBLT; obesity

stigma; structural racism; cultural values; bias within the health care system; provider unfamiliarity with treatment; and lack of availability. She highlighted that a majority of U.S. children (more than 95 percent) were covered by health insurance in 2022 (Conmy et al., 2023). Coverage may be somewhat lower after the end of COVID-19 safety net programs. Because two thirds of all children are enrolled in Medicaid or Medicaid/CHIP, Barlow stated that the role of public insurance programs in access to pediatric obesity treatment is important to consider.

Implementation

Barlow outlined the RE-AIM framework—designed to improve the adoption of interventions through attention to optimizing involving reach, effectiveness, adoption, implementation, and maintenance—and its application to obesity treatment in children. Reach entails examination of patient representativeness of people receiving treatment and of inclusion efforts across sociodemographic and geographic groups. Effectiveness involves assessing the patient outcome in a clinical rather than research setting. Adoption pertains to organizations’ supports and barriers, with consideration given to staff, space, and scheduling requirements. Implementation involves determining the consistency, supports, and monitoring offered by organizations after treatment is adopted. Maintenance considers continuation of treatment. Barlow noted that behavior treatments are often offered to patients free of charge by organizations or foundation-supported programs, so these treatments are not easily sustained.

Barlow said that the AAP CPG identifies evidence from efficacy studies and does not modify key action statements based on the constraints of the health care structure. She added that in so doing, the CPG could motivate changes in policy. Given the prevalence and severity of obesity among U.S. children and the resulting associated chronic health conditions, AOMs should be available in pediatrics, said Barlow. For severe obesity, lifestyle interventions are beneficial but inadequate, she asserted. The price and availability challenges of AOM treatment are similar in pediatric and adult medicine. Although lifestyle support is a component of AOM treatment, it is hard to implement, particularly given the barriers posed by insurance structures, Barlow stated. Future directions include addressing affordability and insurance coverage of AOMs, implementing IHBLT outside of the health care structure, and securing insurance coverage for IHBLT. She noted that CDC is leading IHBLT initiatives and has developed a list of high-quality IHBLTs. Barlow commented on the need for training for primary care pediatricians to prescribe AOMs and ensure appropriate lifestyle support. Additionally, studies are needed of potential mental and physical health harms of AOMs, especially when an AOM is being studied for use in preadolescents or approved for the pediatric population.

However, CPGs using the same staging system, such as the Edmonton Obesity Staging System, are quite similar, he stated. In general, the CPG algorithms and recommendations are fairly consistent, said Ard. Barlow noted that multiple CPGs on pediatric obesity are not available, and therefore the issue of concordance is not yet at play.

CPG Inclusion of Lived Experience

In response to a question about including lived experience in CPG development. Barlow said that a parent representative was part of the AAP CPG writing group. This contribution is of great benefit to providers, as are conference panels of parents and adolescents living with obesity. She underscored that concerns about stigma and bias can make discussing obesity in an office setting intimidating, but input and experiences from patients and parents can be helpful for providers in broaching this topic. Ard noted that Sean Wharton, first author of the Canadian CPG, emphasized that it was for patients and that the standard of care should meet patient expectations for treatment. Ard stated that integrating the patient voice and understanding that patients are a part of the CPG audience are important to developing guidelines; he predicted that the emphasis on lived experience would grow as additional CPGs are developed.

Considerations Regarding Withdrawal of AOM Treatment

Noting that AOM treatment is generally considered to be indefinite, Parekh asked about the scientific basis for this understanding and whether research identifies any potential AOM offramps. Ard replied that evidence indicates that 60–70 percent of adults experience weight regain—either partial or complete—after withdrawal. Moreover, obesity symptoms that often resolve with AOM treatment (e.g., food noise, binge-eating, poor satiation) may return after. Ard explained that patients may return to a mental space that requires expending cognitive energy on behaviors that were easily avoided while on AOMs. More research is needed to understand whether AOM alternatives—such as lowered dosing, less expensive medications, or different classes of medications—can sustain the weight-reduced state. Ard likened replacing AOMs with lifestyle interventions to teaching a person to swim in a shallow pool and then throwing them into the ocean, removing the safety of being able to stand up. He said that the need to shift and reframe an expectation that AOM-induced weight loss will enable patients to successfully navigate the obesogenic environment without AOMs and allow for research through a different lens. Barlow noted that in studies that withdrew AOMs after 12 months in a pediatric population, many participants experienced weight regain. She highlighted the value of efforts to mitigate obesogenic environmental factors to make it easier for individuals to attain improved health.

This page intentionally left blank.