One of the biggest health challenges to humanity, the coronavirus-2019 (COVID-19) pandemic, has changed how we live, work, and interact with each other. Yet, the overwhelming toll that this pandemic has inflicted on our lives and health has obscured the ongoing pandemic of obesity that now affects more than 93 million Americans or more than 39.6% of the population. It is projected that nearly 50% of the US population will suffer from obesity by 2030 (1). Obesity is now the second leading preventable cause of disease and death in the United States, trailing only smoking, with an estimated 300,000 deaths per year attributed to obesity (2). It is also the second leading risk factor, after age, for mortality and intensive care unit admissions in COVID-19 (3). Weight loss can reduce the risk of obesity-associated diseases such as diabetes and nonalcoholic fatty liver disease, but to mitigate and even reverse the progressive course of these, weight loss of 10% or more is needed (4). Sustained weight loss of such magnitude is hard to achieve through lifestyle changes alone: In a large population study, the annual probability of experiencing a 5% weight reduction was 1 in 12 for men and 1 in 10 for women with body mass index (BMI) over 30 kg/m5. Among those who lost weight, 78% gained it back within 5 years (5), consistent with results from other studies.
For patients who fail to achieve and sustain weight loss through lifestyle changes, bariatric surgery should be considered (6). Robust data demonstrate that the weight loss after Roux-en-Y gastric bypass and sleeve gastrectomy is associated with improvements in multiple metabolic disease endpoints and overall mortality (7). Nevertheless, only a small proportion of eligible patients are referred or willing to undergo surgery. In addition, bariatric surgery is usually approved for patients with BMI ≥ 40 kg/m2, or ≥35 kg/m2 with excess weight comorbidities, missing the opportunity to intervene earlier in patients with lower BMIs, before significant metabolic disease is established. Within the Veterans Health Administration (VHA), 78% of veterans have BMI as overweight or obesity, but there are only 21 VHA Bariatric Surgery Programs (8). Thus, there is an urgent need to increase access to obesity treatments for veterans, and this inspired us to spearhead the first VHA-based Bariatric Endoscopy Program.
MINIMALLY INVASIVE AND NONINVASIVE THERAPIES TO THE FOREFRONT
Endoscopic bariatric and metabolic therapies
Since 2015, the US Food and Drug Administration has approved several endoscopic bariatric and metabolic therapies (EBMTs) that can be used in patients with BMI > 30 kg/m2, which could potentially address the treatment gap for patients with lower weights. These fall into 3 categories: (i) space-occupying devices (gastric balloons and transpyloric shuttle), (ii) aspiration therapy, and (iii) gastric remodeling such as endoscopic gastroplasty (US Food and Drug Administration-approved for tissue apposition, used for remodeling of the stomach anatomy to achieve weight loss) (9). The reported weight loss with the available EBMTs ranges from about 10% (gastric balloons) to 14% (aspiration therapy) to 16% (endoscopic gastroplasty), with a low rate of serious adverse events (10–12), Figure 1. These results reach or are higher than the 10% weight loss target needed to reverse liver fibrosis or decrease the risk of myocardial infarction.
Obesity pharmacotherapy has increasingly become accessible and effective as an adjunct to augment lifestyle intervention and as a strategy to maintain weight loss after EBMTs (13). Agents can be classified as peripherally acting agents that prevent nutrient absorption (e.g., orlistat), appetite-suppressant medications (e.g., phentermine/topiramate), and weight-negative incretin mimetics such as GLP-1 agonists (e.g., liraglutide). Most agents, except orlistat, have central nervous system effects to suppress appetite in the hypothalamic center regulating hunger. These agents cause modest weight loss ranging from 3 to 6 kg at 1 year. A challenge for the field is maintaining weight and de-escalating pharmacotherapy once the patient's weight goal has been achieved.
What are some of the advantages of less invasive treatments?
EBMTs such as gastric balloons and aspiration therapy are not technically challenging and are similar to commonly performed procedures, thus allowing greater uptake among gastroenterologists and increased access for patients; they are available for patients with lower BMI (30–40 kg/m2 for balloons and 35–55 kg/m2 for aspiration therapy); and they appeal to patients because they are perceived as less invasive than surgery. Although less common than with surgery, serious adverse events and mortality have been noted (Figure 1). Weight regain is also an issue. Thus, EBMTs should not be undertaken lightly. Judicious selection of patients and close follow-up after the procedure are requisite. A multidisciplinary team approach that may include a medical bariatrician, psychologist, dietitian, exercise physiologist, and surgeon is essential for improved outcomes (Figure 2).
Similar considerations apply to weight loss pharmacotherapy. If clinically meaningful weight loss is not achieved with lifestyle interventions, addition of pharmacotherapy is indicated to change the inherent weight set-point trajectory to maximum weight (6). Patient selection for pharmacotherapy requires a detailed evaluation focusing on excess weight comorbidities, potential contraindications, and side effects. However, patient response is variable and often requires multiple agents to target the redundant protective pathways that regulate hunger and drive weight gain (14). Finally, the long-term effects of obesity pharmacotherapy agents beyond the year-long outcomes reported from pivotal trials remain to be determined. In this context, obesity pharmacotherapy and bariatric endoscopy represent a contiguous part of the spectrum of chronic obesity care before bariatric surgery, with initial data supporting a synergistic effect (13).
The multidisciplinary team
With these considerations in mind, in 2015, we started the first VHA-based Bariatric Endoscopy Program combining EBMTs and pharmacotherapy in collaboration with the VA MOVE! Program. Our treatment algorithm takes into account the chronic nature of obesity, the risk of weight regain after any intervention, including surgery, and the need to support our patients over time. The VHA provides a unique opportunity to create such a model because most of the EBMTs and weight loss medications are covered for veterans. Outside of the VHA, this may present additional challenges because of the current cash-pay model for most EBMTs and weight loss pharmacotherapy.
The patients undergo a multidisciplinary work-up that includes evaluations by a registered dietitian and a psychologist, participation in information sessions to review all weight loss options, discussions with the primary care physician, the bariatric endoscopist, and the endocrinologist to select the optimal treatment plan (Figure 2). Patients are also seen by other services to diagnose and treat comorbid conditions such as sleep apnea and cardiovascular disease. It is expected that the patients would go through a trial of lifestyle intervention with caloric restriction and patient education by a dietitian before selecting an initial intervention, whether it is an EBMT such as a gastric balloon, pharmacotherapy, or surgery (Figures 2 and 3). Depending on the type of therapy selected, this first treatment cycle can last from 3 to 12 months or more, with ongoing support from the multidisciplinary team and reassessment every 3–6 months.
Multiple treatment cycles
If patients have not achieved their weight loss goals with the initial treatment, a new strategy is selected. This could entail a different weight loss medication or a procedure such as aspiration therapy, endoscopic gastroplasty, or surgery (Figure 3). In subsequent cycles, we can add more medications, consider a different EBMT, or maintain the patient's current course of treatment. Medications can be used concurrently or sequentially with EBMTs. From the start, our patients are made aware that this is a long-term program and that active participation in lifestyle and behavioral sessions is the key to success. Our aim is to demonstrate that the various EBMTs and medications are simply tools that augment and improve adherence to lifestyle changes.
Many novel weight loss modalities are currently under investigation, including a procedureless balloon, plication devices, small bowel therapies, and medications targeting simultaneously multiple pathways. These new therapies can improve our ability to optimize and personalize treatments. Another direction is the application of an integrated care model, such as the patient-centered medical home, to the long-term management of obesity in the VHA and elsewhere.
The multidisciplinary stepped-care approach and ongoing conversation between providers and patients allows us to create an environment in which our patients feel supported and eager to participate. Our versatile approach gives the practitioner more options to respond to the patient's progress or lack thereof. Initial results support our strategy (15). Going forward, we intend to collect long-term data to evaluate whether this combined plan of EBMTs, pharmacotherapy, and behavioral interventions can achieve sustained improvement, similar to surgery, in patients' health outcomes, reduce the burden of metabolic diseases, and attenuate the course of diseases affected by obesity, such as COVID-19.
CONFLICTS OF INTEREST
Guarantor of article: Violeta B. Popov, MD, PhD, FACG.
Specific author contributions: V.B.P.: conceptualized this manuscript, design, revisions, and completed the first and revised drafts of the manuscript. A.A.: contributed to conception and critical review. J.O.A.: contributed to the conception, writing, and review of the manuscript.
Financial support: None to report.
Potential competing interests: V.B.P.: consultancy fees, Obalon; research support: Microtech. J.O.A. and A.A.: None to report.
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