**Background:** This 2022 Clinical Practice Statement (CPS) from the Obesity Medicine Association (OMA) provides clinicians with an overview of FDA-approved anti-obesity medications and investigational agents. It is part of a series derived from the OMA Obesity Algorithm, designed to assist in the care of patients with pre-obesity/obesity. The statement emphasizes that anti-obesity medication treatment is one of four nonsurgical pillars of obesity management, alongside nutrition, physical activity, and behavior. Weight reduction of as little as 5–10% (or 3% in some cases) can improve adiposopathy and fat mass disease. The purpose of these medications includes serving as an adjunct to lifestyle interventions, treating sick fat disease, slowing weight regain, and improving health and quality of life.
**Methods:** The scientific information is based on published citations, clinical perspectives of OMA authors, and peer review by OMA leadership. The statement covers pharmacokinetic principles applicable to obesity, including drug absorption, metabolism, distribution, and excretion. It discusses the efficacy and safety of approved medications such as phentermine, semaglutide, liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and non-systemic superabsorbent oral hydrogel particles (classified as a medical device). Other medications covered include setmelanotide, metreleptin, and lisdexamfetamine dimesylate. Data on combination pharmacotherapy and use after bariatric surgery are also reviewed, along with investigational agents, particularly tirzepatide.
**Key Results:** The statement provides detailed efficacy data for each medication. For example, semaglutide 2.4 mg subcutaneously once weekly yields a mean weight reduction of approximately 15%, with 86% of patients achieving ≥5% weight loss, 69% achieving ≥10%, 51% achieving ≥15%, and 32% achieving ≥20%. Liraglutide 3.0 mg daily results in a mean weight reduction of about 8%, with 63% achieving ≥5% and 33% achieving ≥10%. Phentermine/topiramate extended release (top dose) shows a mean weight reduction of 9–10%, with 66–79% achieving ≥5% and 41–54% achieving ≥10%. Naltrexone/bupropion yields a mean weight reduction of about 7%, with 56% achieving ≥5% and 27% achieving ≥10%. Orlistat 120 mg three times daily produces a mean weight reduction of about 9%, with 66% achieving ≥5% and 39% achieving ≥10%. The non-systemic oral hydrogel results in a mean weight reduction of about 6%, with 59% achieving ≥5%. For the investigational agent tirzepatide, the 15 mg dose shows a mean weight reduction of approximately 21%, with 91% achieving ≥5% and 57% achieving ≥20%. The statement also reviews pharmacokinetic considerations, such as the impact of obesity on drug absorption (e.g., reduced subcutaneous blood flow) and the importance of protein binding (e.g., semaglutide is >99% bound to albumin). It highlights that phentermine is contraindicated in cardiovascular disease and uncontrolled hypertension, while GLP-1 receptor agonists (semaglutide, liraglutide) are contraindicated in patients with personal or family history of medullary thyroid cancer or type 2 multiple endocrine neoplasia.
**Clinical Implications:** The statement emphasizes that anti-obesity medications should be used as adjuncts to lifestyle interventions and that individual patient response should guide continuation or discontinuation. It notes that if no clinical improvement (e.g., at least 3–5% loss of baseline body weight) occurs after 12–16 weeks, the prescribing information may recommend increasing the dose or discontinuing the medication. The statement also discusses the potential for combination therapy and use after bariatric surgery, though data are limited. It highlights that anti-obesity drug development is following the path of other metabolic diseases, where cardiovascular outcome benefits will likely transform these medications into standards of care. The statement concludes that this CPS is designed to assist clinicians in the care of patients with pre-obesity/obesity, with the anticipation that newer agents will provide additional safe and effective treatments.