Obesity currently affects more than 40% of the U.S. population. It is the second-leading preventable cause of mortality behind smoking with an estimated 300,000 deaths per year.1,2 Weight loss can reduce the risk of metabolic comorbidities such as diabetes, heart disease, and stroke. However, 5%-10% total body weight loss (TBWL) is required for risk reduction.3 Sustained weight loss involves dietary alterations and physical activity, although it is difficult to maintain long term with lifestyle changes alone. Less than 10% of Americans with a BMI greater than 30 kg/m2 will achieve 5% TBWL each year, and nearly 80% of people will regain the weight within 5 years, a phenomenon known as “weight cycling.”4,5 Not only can these weight fluctuations make future weight-loss efforts more difficult, but they can also negatively impact cardiometabolic health in the long term.5 Thus, additional therapies are typically needed in conjunction with lifestyle interventions to treat obesity.
Current guidelines recommend bariatric surgery for patients unable to achieve or maintain weight loss through lifestyle changes.6 Surgeries like Roux-en-Y gastric bypass and sleeve gastrectomy lead to improvements in morbidity and mortality from metabolic diseases but are often only approved for select patients with a BMI of at least 40 or at least 35 with obesity-related comorbidities.7 These restrictions exclude patients at lower BMIs who may have early metabolic disease. Furthermore, only a small proportion of eligible patients are referred or willing to undergo surgery because of access issues, socioeconomic barriers, and concerns about adverse events.8,9 Endoscopic bariatric therapy and antiobesity medications (AOMs) have blossomed because of the need for other less-invasive options to stimulate weight loss.
Minimally invasive and noninvasive therapies in obesity
Endoscopic bariatric and metabolic therapies
Endoscopic bariatric and metabolic therapies (EBMTs) are used for the treatment of obesity in patients with a BMI of 30 kg/m2, a cohort that may be ineligible for bariatric surgery.10,11 EBMTs involve three categories: space-occupying devices (intragastric balloons [IGBs], transpyloric shuttle [TPS]), aspiration therapy, and gastric remodeling (endoscopic sleeve gastroplasty [ESG]).21,13 Presently, TPS and aspiration therapy are not commercially available in the United States. There are three types of IGB approved by the Food and Drug Administration, and Apollo ESGTM recently received de novo marketing authorization for the treatment of obesity. TBWL with EBMTs is promising at 12 months post procedure. Ranges include 7%-12% TBWL for IGBs and 15%-19% for ESG, with low rates of serious adverse events (AEs).13-18 Weight loss often reaches or exceeds the 10% TBWL needed to improve or completely reverse metabolic complications.
Multiple professional societies support the use of obesity pharmacotherapy as an effective adjunct to lifestyle interventions.19 AOMs are classified as peripherally-acting to prevent nutrition absorption (e.g. orlistat), centrally acting to suppress appetite and/or cravings (e.g., phentermine/topiramate or naltrexone/bupropion), or incretin mimetics such as glucagonlike peptide–1 agonists (e.g., liraglutide, semaglutide).20 With the exception of orlistat, most agents have some effects on the hypothalamus to suppress appetite.21 Obesity medications tend to lead to a minimum weight loss of 3-10 kg after 12 months of treatment, and newer medications have even greater efficacy.22 Despite these results, discontinuation rates of the popular GLP-1 agonists can be as high as 47.7% and 70.1% at 12 and 24 months, respectively, because of the high cost of medications, gastrointestinal side effects, and poor tolerance.23,24