Medications for Obesity: Key Points

The following are key points to remember from a review of medications used to treat obesity:

1. The Food and Drug Administration (FDA) has approved multiple antiobesity medications (AOMs) with indications to treat adults with a body mass index (BMI) of ≥30 kg/m2 or a BMI of ≥27 kg/m2 in addition to weight-related comorbidities such as type 2 diabetes, hypertension, or dyslipidemia. AOMs are also indicated to treat obesity in adolescents aged 12-17 years with a BMI at or above the 95% percentile for age and sex.
2. AOMs are classified into three main groups based on their mechanism of action including intra-gastrointestinal (intra-GI) medications, centrally acting medications, and nutrient-stimulated hormone-based medications.
3. Orlistat, the only FDA-approved intra-GI agent, works by blocking digestion and absorption of approximately 30% of dietary fat in the stomach and small intestine. Although most guidelines support use of orlistat in treatment of obesity, the American Gastroenterological Association recommends against its use due to its small effect on weight loss and adverse GI effects. Although orlistat’s effect on weight loss is modest, it has also been shown to lower systolic blood pressure (BP), glycated hemoglobin (HbA1c), and low-density lipoprotein (LDL) cholesterol and has been associated with prevention of type 2 diabetes.
4. Centrally acting AOMs include phentermine, phentermine-topiramate, and naltrexone-bupropion. These medications have various mechanisms of action in the brain that result in reduced appetite.
5. Phentermine is only approved for short-term use (up to 3 months) and is recommended in patents without cardiovascular disease. Although few studies have evaluated the efficacy and safety of phentermine beyond 3 months, few or no serious adverse events occurred in available studies with a duration of 6 months or longer. Phentermine is the least expensive AOM for patients with no insurance coverage.
6. Long-term phentermine-topiramate can achieve and sustain a 10% weight reduction and observational data has found no association between this AOM and adverse cardiovascular events. Weight reduction with naltrexone-bupropion is greater when combined with intensive behavioral therapy and BP should be monitored closely during initiation and dose escalation since bupropion is known to increase BP.
7. Three nutrient-stimulated hormone-based AOMs are currently FDA-approved: liraglutide, semaglutide, and tirzepatide. In addition to weight loss, liraglutide has shown decreases in HbA1c and major adverse cardiovascular events in patient with type 2 diabetes.
8. Semaglutide and tirzepatide have both shown greater weight reductions than other AOMs including liraglutide. Additionally, these agents are associated with improved cardiometabolic outcomes including HbA1c, BP, and waist circumference. Semaglutide has also been shown to improve heart failure symptoms and increase 6-minute walk distance in patients with heart failure with preserved ejection fraction.
9. All AOMs are approved as adjunctive therapy to lifestyle modifications including a reduced-calorie diet and increased physical activity. The US Preventive Services Task Force recommends behavioral therapy in conjunction with AOMs to improve outcomes.
10. Patients should be counseled to integrate resistance training to minimize loss of lean body mass and enhance functional strength and mobility. AOMs should be used with caution in older adults with low lean body mass due to aging.
11. Real-world studies have shown poor AOM adherence and weight gain is common when medications are discontinued. Clinicians should employ shared decision making to determine medication duration including continuing the lowest effective dose, using intermittent therapy, or stopping medication and closely monitoring weight.

https://jamanetwork.com/journals/jama/article-abstract/2821290