The fight against obesity: Understanding combination pharmacological treatments
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Obesity is a multifactorial disease most effectively treated with a multifactorial approach.
While weight loss programs and advertisements often claim to offer quick fixes, successful obesity management is typically not achieved through a one-size-fits-all strategy. Instead, long-term success is best achieved via a patient-centered approach that utilizes a variety of personalized, evidenced-based approaches.
As with treatment of other metabolic diseases, anti-obesity medication is a safe and effective treatment option in our fight against obesity. Anti-obesity medications may reduce hunger, increase satiety and, in some cases, affect how nutrients undergo gastrointestinal absorption and metabolism. However, the effectiveness of anti-obesity medications is widely variable. As such, patients achieve optimal health benefits when anti-obesity medications are utilized as an adjunct to healthful nutrition, routine physical activity, and favorable behavior modification.
Given the rapid research advancements, it is important clinicians stay up-to-date on the latest anti-obesity medications and pharmacological treatment combinations to provide patients with a holistic understanding of treatment options that can help patients with obesity reach their health goals.
An overview of anti-obesity medications
Anti-obesity medications are generally indicated for adults with a BMI of 30 kg/m2 or greater, or adults with a BMI of 27 kg/m2 or more and having adverse consequences of obesity, such as type 2 diabetes, hypertension or dyslipidemia. Common anti-obesity medications prescribed by clinicians include phentermine, semaglutide, liraglutide, phentermine/topiramate combination agent, naltrexone/bupropion combination agent and orlistat.
Understanding pharmacological treatment combinations
The amount of clinical trial data supporting combination anti-obesity medications is less than the data regarding combination treatment of other metabolic diseases. The data are summarized in a 2022 Obesity Medicine Association Clinical Practice Statement, which provides an overview of FDA-approved anti-obesity medications and investigational anti-obesity agents in development. Unless already a combination anti-obesity drug (e.g., phentermine/topiramate or naltrexone/bupropion), anti-obesity agents usually do not have specific indicated uses to prescribe as combination therapy. But that is not to say that such combinations are contra-indicated. Currently, pharmacological treatment combinations fall into three categories:
Combining with other medications
Anti-obesity medications with indicated uses to treat obesity can be combined with other medications that, while not specifically indicated to treat obesity, promote weight reduction. For example, anti-obesity medication such as a glucagon-like peptide 1 receptor agonists (liraglutide or semaglutide) have been combined with drugs such metformin or sodium/glucose transporter 2 inhibitors.
Combining two anti-obesity medications
Another approach is the use of two different approved anti-obesity medications. As before, while such an approach is common for the treatment of diabetes, hypertension and dyslipidemia, the clinical trial evidence supporting such an approach for obesity is limited.
Combining with bariatric surgery
Some evidence supports that anti-obesity medications may mitigate weight regain after bariatric surgery, which can be considered a type of combination treatment for obesity.
Considerations for combining treatments
While BMI is the primary criterion that helps determine who is eligible to receive anti-obesity medications (i.e., consistent with indicated use), BMI is not the sole consideration. The decision to use combination anti-obesity therapies should be determined based on the entirety of the patient presentation, including proper diagnosis (i.e., performing body composition analyses in patients with suspected increase in muscle mass or, conversely, sarcopenia); complications of obesity; use of other prescription medications; the anticipated safety and efficacy of a particular combination treatment; and patient agreement.
Potential complications and risks to consider
Decisions regarding the use of combination anti-obesity therapy, and the choice of combination therapy, should include the anticipated safety and efficacy of a particular combination treatment. For example, the prescribing information for phentermine indicates that the safety and efficacy of its combination with other anti-obesity agents have not yet been established. At a minimum, phentermine should not be used alone or in combination in patients with cardiovascular disease — for which phentermine is contraindicated. An exception would be the use of the phentermine/topiramate combination agent, which is not contraindicated in patients with CVD.
While more data on pharmacological treatment combinations are collected, clinicians should stay updated on the latest research regarding the safety and effectiveness of anti-obesity therapies, and through a patient-centered approach, choose the best anti-obesity medication for the individual patient.
Our knowledge of anti-obesity medications is rapidly evolving. To access the latest obesity research, resources, and tools, become a member of the Obesity Medicine Association (OMA). To learn more or join, visit obesitymedicine.org and/or Obesity Pillars, the official publication of the OMA.