Progress in Pharmacotherapy for Obesity
Susan Z. Yanovski et al.
The obesity epidemic in the US continues unabated. The elevated risk for severe disease and death from COVID-19 associated with obesity and its comorbidities underscores the urgency to develop and implement effective prevention and treatment strategies. Multicomponent behavior-based weight management interventions are recommended for adults with obesity; however, some patients do not respond to even the highest-quality programs. Medications are wellaccepted in themanagement of other disorders that potentially respond to dietary interventions, suchas the use of statin drugs for hypercholesterolemia.However,many clinicians are hesitant to prescribe, payers are hesitant to reimburse for, and patients are hesitant to use antiobesity medications. There are numerous reasons for such hesitancy. Antiobesity medications have a problematic safety history, with several drugs removed from themarket for adverse events. Weight losses with antiobesity medications rarely meet patient expectations. Also, physicians prescribe antiobesity medications infrequently relative to the numbers of adults who are potentially eligible for their use. According to national estimates, only 3% of adults trying to lose weight reported taking prescription antiobesity medications between 2012 and 2016. Many private and public payers do not cover antiobesitymedications at all or require prior authorization, and the majority of patients receiving prescription obesity medications pay out of pocket. Currently Approved Antiobesity Medications As of June 2021, a total of 5 medications (orlistat, phentermine plus topiramate, naltrexone plus bupropion, liraglutide,andsemaglutide)arecurrentlyapprovedby the US Food and Drug Administration for long-term weight management in adults with body mass index of at least 30 or body mass index of at least 27 and comorbid conditions (eTable in the Supplement). The notable additions to the medications that were approved by 20151,2 are daily subcutaneous liraglutide, 3.0 mg, a glucagonlike peptide-1 (GLP-1) receptor agonist that has been shown to reduce body weight by approximately 5 kg (approximately 5% of body weight) more than placebo inadults3,4and thoseaged 12 to 17years,5 andweekly subcutaneous semaglutide, 2.4 mg.6-9 In addition, setmelanotide,amelanocortinagonist,was approved in 2020 for treatment of syndromes of genetic obesity affecting the proximal leptin-signaling pathway in adults and children 6 years or older. Because of the rarity of such syndromes, setmelanotide was approved without longterm placebo-controlled clinical trials, but with evidence of substantial effects on body weight.