Obesity and overweight affect a growing proportion of adults worldwide, with global estimates suggesting that 43% of adults are living with overweight and 16% with obesity. In the United States, estimates indicate that 40.3% of American adults are living with obesity, and nearly three-quarters of adults are living with overweight or obesity.
Having excess weight is associated with an increased risk of conditions such as type 2 diabetes, high blood pressure, cardiovascular disease, and some cancers.
In recent years, newer weight-loss medications, particularly those belonging to the glucagon-like peptide-1 (GLP-1) receptor agonist class and related therapies, have transformed obesity treatment. However, questions have remained about how clinicians should prioritize the growing number of available options.
Now, new clinical guidelines from the American College of Physicians (ACP) recommend the medications containing semaglutide, such as Ozempic and Wegovy, and tirzepatide, such as Mounjaro and Zepbound, as the preferred first-line drug treatments for adults with obesity, when used alongside lifestyle changes.
The guidance, published in the Annals of Internal Medicine, alongside a patient summary, is designed to help physicians navigate the rapidly evolving landscape of obesity medications. The ACP has designated the document a ‘living guideline,’ noting they will update the guidance as new evidence emerges.
For nonpregnant adults with obesity, which is defined as a body mass index (BMI) of 30 kg/m² or higher, the ACP recommends semaglutide and tirzepatide as first-line pharmacologic treatments.
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They also emphasize that these medications should be combined with lifestyle modifications, such as improved nutrition and increased physical activity.
“These medications are currently the most effective pharmacologic options for obesity management,” Mir Ali, MD, a bariatric surgeon, bariatric medicine specialist, and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, told Medical News Today.
“However, it is important to note that surgical weight loss procedures still offer a higher long-term success rate for those who qualify.”
Ali was not involved with creating the new guideline.
The guideline also ranks phentermine-topiramate, liraglutide, and naltrexone-bupropion as second-, third-, and fourth-line options, respectively.
For adults with overweight, defined as BMI between 27 and 30 kg/m², and at least one obesity-related condition, such as type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease, the ACP again recommends semaglutide or tirzepatide as first-line options. However, for this group, the ACP recommends liraglutide as a second-line treatment.
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The recommendations are based on evidence reviews commissioned by the organization that evaluated both the benefits and potential harms of available obesity medications, as well as their cost-effectiveness.
Semaglutide and tirzepatide have consistently demonstrated greater weight-loss effects than other therapies in clinical trials, contributing to their designation as preferred first-line options.
“The most important takeaways are that semaglutide and tirzepatide, combined with lifestyle modifications, are now considered first-line pharmacologic options for patients with a BMI over 30, or a BMI over 27 with comorbid conditions such as diabetes or hypertension,” Ali highlighted.
The ACP guideline also emphasizes that medication decisions should not be based solely on expected weight loss.
They encourage healthcare professionals and patients to discuss a range of factors, including potential benefits and harms, treatment costs, medication availability, existing health conditions, personal goals, life expectancy, and patient preferences.
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“It is essential for patients to understand the mechanism of action, potential side effects, and benefits of these treatments, as well as the likelihood that long-term therapy will be necessary,” Ali emphasized to MNT.
“Furthermore, these medications should be viewed as tools to help patients adapt to a healthier diet and lifestyle to achieve optimal results.”
The organization also highlights the importance of monitoring for unintended consequences of weight loss treatment.
These may include nutritional deficiencies, as well as reductions in muscle mass and bone density, which are concerns that may be particularly relevant for older adults.
A notable aspect of the ACP document is its status as a living guideline. Unlike other clinical guidance, which may often remain unchanged for years, living guidelines are updated as new evidence becomes available.
This approach is particularly important in obesity medication, as research is progressing rapidly and new medications continue to enter clinical practice.
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“The primary benefit of a living guideline is that recommendations can be updated as new data becomes available. This is a significant improvement over traditional static guidelines, which may not change for many years.”
– Mir Ali, MD
For those seeking medical treatment for obesity, the guideline signals a growing consensus that newer anti-obesity medications, such as GLP-1 and incretin-based therapies, can play an important role alongside dietary changes, regular physical activity, and other lifestyle interventions.
However, it is important that treatment decisions remain individualized. Factors such as medical history, side effects, affordability, access to medications, and personal treatment goals are key considerations when determining the most appropriate therapy.
As additional evidence emerges, the ACP’s living guideline is expected to continue evolving, potentially reshaping how obesity and overweight are managed in clinical practice in the years ahead.
“The key message is that medications can be an excellent tool to help patients achieve and maintain long-term dietary and lifestyle changes.”
