Choosing the right medication for obesity treatment: Factors to consider

Managing obesity involves a well-rounded approach, often including lifestyle modifications and, in many cases, pharmacotherapy. Understanding the role of anti-obesity medications is crucial in this context.

The primary goal of using medications in obesity management is to effectively treat this chronic disease by reducing excess body weight. In doing so, these medications aim to alleviate associated metabolic comorbidities such as diabetes, hypertension and dyslipidemia. They are typically prescribed for adults with a BMI of 30 kg/m² or greater, or for those with a BMI exceeding 27 kg/m² who also experience adverse consequences of obesity. This approach improves overall health outcomes and enhances the quality of life for individuals with obesity.

According to the Obesity Medicine Association (OMA) Obesity Algorithm, treatment for obesity revolves around four key pillars: nutrition therapy, physical activity, behavioral modification and medical interventions. Among these, medical interventions, including anti-obesity medications, play a pivotal role in targeting the physiological mechanisms that contribute to weight gain.

Available medications and how they work

Anti-obesity medications work in various ways to promote weight loss. Many medications primarily target central pathways in the brain that regulate appetite and satiety. For instance, phentermine, a widely used sympathomimetic amine, suppresses appetite by acting on neurotransmitter systems in the brain. Similarly, Qsymia (phentermine and topiramate, Vivus) and Contrave (bupropion and naltrexone, Currax) work on appetite suppression and energy expenditure through different pathways.

Newer injectable medications like Wegovy (semaglutide, Novo Nordisk), Zepbound (Tirzepatide, Lilly) and Saxenda (Liraglutide, Novo Nordisk) are synthetic peptides that act as glucagon-like peptide receptor (GLP-1) agonists, affecting appetite control centrally and insulin secretion peripherally. These medications represent a significant advancement, offering substantial weight-loss benefits and even showing cardioprotective effects in certain populations.

The landscape of anti-obesity medications is diverse, with options ranging from oral medications like phentermine and its combinations to injectables such as GLP-1 analogs and gastrointestinal lipase inhibitors like orlistat. These medications vary in efficacy and side-effect profiles but collectively aim to achieve meaningful weight reduction ranging from 5% to 22% of total body weight, depending on the specific medication and patient response.

Phentermine and topiramate is a combination that is FDA approved for chronic weight management in eligible adolescents aged older than 12 years and in adults with excess weight and usually offers 5% to 10% weight reduction.

The combination of naltrexone and bupropion is also indicated for chronic weight management and offers 5% weight reduction. Naltrexone is an opioid antagonist and should not be used in patients with chronic opioid use. Bupropion is an antidepressant and is contraindicated in patients with seizure disorder.

Liraglutide is a GLP-1 analog given as a daily injectable, offering average weight reduction of 5% to 10% in adults with obesity. It is also FDA approved for chronic weight management in pediatric patients aged older than 12 years with a BMI exceeding the 95th percentile.

Semaglutide is one of the first highly effective anti-obesity medications. It is a weekly subcutaneous injection starting at a dose of 0.25 mg and increasing every 4 weeks to reach a maintenance dose of either 1.7 mg or 2.4 mg per week. Semaglutide recently received another FDA approval for its cardioprotective role in secondary prevention of adverse cardiovascular events in patients with established cardiovascular disease like coronary artery disease and stroke. It can help patients achieve approximately 16% weight loss.

Tirzepatide is the newest and most effective FDA-approved anti-obesity medication, which has demonstrated a mean weight reduction of 20.9%. It is a dual peptide. It is also once-weekly subcutaneous injection. The starting dose for tirzepatide is 2.5 mg, and the doses are increased by 2.5 mg every 4 weeks depending upon how it is tolerated.

Orlistat is an FDA approved anti-obesity medication that works as a gastrointestinal lipase inhibitor. It provides caloric restriction by not letting fats from dietary intake to be absorbed in the intestines.

The importance of tailoring treatment

Health care providers should tailor medication therapy based on individual patient needs, considering factors like comorbidities, contraindications and patient preferences. The decision to prescribe an anti-obesity medication typically hinges on criteria such as BMI and the presence of obesity-related complications like diabetes or hypertension. Regular monitoring is essential to assess efficacy, safety and tolerability, ensuring that adjustments can be made as needed to optimize outcomes.

Additionally, providers must be mindful of potential drug interactions and side effects unique to each medication. For example, GLP-1 analogs may affect the absorption of oral contraceptives, necessitating careful consideration in reproductive-aged women.

Part of effective obesity management involves considering the impact of other medications on weight gain. Many commonly prescribed drugs for conditions like diabetes, depression and hypertension can contribute to weight gain. Providers should evaluate the potential benefit of switching to weight-neutral or weight-reducing alternatives where possible, thereby supporting overall weight management efforts.

Resources for health care providers

For health care providers seeking comprehensive resources on medications for obesity treatment, the Obesity Medicine Association (OMA) offers valuable tools such as:

• The OMA’s clinical practice statement on anti-obesity medications, published in Obesity Pillars;
• Obesity Algorithm; and
• OMA Blog.

These resources provide evidence-based guidelines, treatment algorithms and updates on emerging therapies, facilitating informed decision-making in clinical practice.

Although anti-obesity medications represent a critical component of comprehensive obesity management, they are most effective when integrated into a holistic treatment approach that includes lifestyle modifications and ongoing patient support. By understanding their mechanisms, tailoring therapies to individual needs and staying informed with reliable resources, health care providers can optimize outcomes for patients navigating the challenges of obesity.

References:

• Aronne LJ, et al. JAMA. 2024;doi:10.1001/jama.2023.24945.
• Bays HE, et al. Obes Pillars. 2022;doi:10.1016/j.obpill.2022.100018.

For more information:

Anila Chadha, MD, DABOM, is a family physician and obesity medicine physician at Dignity Health Medical Group in Bakersfield, California, and the obesity medicine director at Mercy Weight Loss Surgery Program in Bakersfield, California.