Glucagon-like peptide receptor agonists (GLP-1 RAs) now available to promote weight loss—Wegovy (semaglutide), Zepbound (tirzepatide), and Saxenda (liraglutide)—could potentially make much needed gains against the obesity epidemic; however, the benefits of these medications come at a significant financial cost to patients and payors and the risk of rare but serious adverse events. Making sure the medications reach the right patients—those most likely to derive long-term benefits with low risk—will be critical to make the most of GLP-1 RAs. Prescribers will lead that effort by identifying and recruiting eligible patients, which is a difficult task because obesity is a complex disease; therefore, prescribing information will need to be interpreted in the context of each patient’s unique characteristics and circumstances. Furthermore, old and new misconceptions about obesity and weight loss drugs—now amplified and reinforced by social trends and media—can predispose patients and make discussions with physicians difficult.

Understanding the background and evidence behind labeled indications may help prescribers assess patients’ needs and manage their concerns and expectations. To that end, ECRI’s recently published evidence report, Best Clinical Practices for Managing Obesity and Overweight with GLP-1 Receptor Agonists, reviewed contemporary clinical practice guidance from medical societies and public health agencies along with the best available clinical evidence on GLP-1 RA safety and effectiveness. We identified and reviewed eight evidence-based guidelines, seven consensus-based guidance documents, seven meta-analyses of randomized controlled trials (RCTs), and eight additional RCTs.

Our special report’s key findings include the following:

• Labeled indications for GLP-1 RAs (i.e., patients with body mass index [BMI] ≥30 kg/m2 or ≥27 kg/m2 with obesity-related comorbidities) follow a longstanding consensus established by the National Heart, Lung, and Blood Institute’s 1998 guidelines on obesity management. Later clinical trials adopted these criteria for patient inclusion, which subsequent evidence-based guidelines then reflected. FDA adopted similar criteria in 2007.
• The 1998 consensus incorporates the clinical evidence available at the time—in particular, a 1995 U.S. real-world study that found limited benefits for weight loss in women with BMI between 27 and 30 kg/m2 and no comorbidities. The 1998 guideline authors concluded that the risks associated with weight loss drugs available at the time (sibutramine, fenfluramine, and phentermine) are likely to outweigh potential benefits in otherwise healthy, nonobese patients with overweight.
• Clinical trials of liraglutide, semaglutide, and tirzepatide for weight loss also followed these criteria and provide conclusive evidence supporting the drugs’ safety and effectiveness in adults and adolescents (age >12) used according to the labeled indications. The studies also demonstrate that GLP-1 RAs are safe and effective for weight loss in patients with severe mental illness treated with antipsychotic medication.
• A few RCTs also reported favorable results in patients with poor weight loss or weight regain after bariatric surgery and in patients with severe heart failure, but more studies are needed to confirm those findings.
• To engage patients about weight loss, the Centers for Medicare & Medicaid Services and U.S. medical societies recommend adopting a patient-centric perspective and a structured approach with the 5-A Framework: determine the optimal timing for discussion (“Ask”), evaluate the patient’s need and priorities (“Assess”), counsel the patient on weight loss benefits and options (“Advise”), make joint decisions on treatment and goals (“Agree”), and identify and deliver needed support (“Assist”).  

Many patients inquiring about GLP-1 RAs may not be good candidates for pharmacotherapy; however, the consultations represent a valuable opportunity to recruit these patients into evidence-based treatment. For eligible patients, dispelling misconceptions can help patients stay motivated into making long-lasting lifestyle changes. ECRI’s special report also discusses how clinicians may leverage the evidence to engage patients about GLP-1 treatment by presenting typical scenarios that many prescribers can expect to encounter given public perceptions about obesity and weight loss medications. Last, directing patients to reliable information sources is more important than ever to counter the effects of misinformation and hype in social media and their deleterious effects on patient-physician relationships.

ECRI members may access this report in its entirety here. Non-members may register to receive a copy of the report.