“I have tried everything, and nothing works.”
This comment can be a common theme for the nearly one-half of all Americans who engage in unsuccessful weight-loss efforts every year. The exploding popularity and dramatic results achieved by a new class of “diet drugs” have led to an increased demand for these medications, including those intended for other purposes.
Nearly 75% of U.S. adults are overweight, according to the U.S. Centers for Disease Control and Prevention (CDC), and 4 out of 10 adults and 1 out of 5 children and adolescents are obese. The CDC estimates that obesity added $173 billion to U.S. healthcare expenses in 2019.
In 2023, the U.S. Food and Drug Administration (FDA) approved two additional drugs—Wegovy (semaglutide) and Zepbound (tirzepatide)—to treat overweight and obese individuals. These medications are designed to help people eat less and lose more weight by slowing the movement of food from the stomach and affecting brain signals that control hunger.
Together with Saxenda (liraglutide)—FDA-approved in 2014—Wegovy and Zepbound are glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which are drugs that lower blood sugar levels by regulating the release of insulin and glucagon. In addition, the off-label use of Ozempic (semaglutide), Mounjaro (tirzepatide), and Victoza (liraglutide)—similar drugs whose primary purpose is treating diabetes—have caused shortages of these three drugs, affecting patients who need them for blood sugar control.
A large body of clinical evidence supports that GLP-1 RAs can help people lose 15% to 25% additional weight when used with lifestyle changes, such as counseling, diet, and exercise. These effects are greater than those seen with older weight-loss medications—typically about 5% total weight loss—and close to typical weight loss seen with bariatric surgery.
ECRI and the Institute for Safe Medication Practices (ISMP) have conducted extensive research into the effectiveness of such medications, including a recently published evidence report, Best Clinical Practices for Managing Obesity and Overweight with GLP-1 Receptor Agonists. This report examines clinical evidence, clinical practice guidelines, and selected additional resources to provide context on GLP-1 RA use for overweight and obesity management. The report also aids prescribers on patient selection, treatment, and adverse event monitoring, along with support for lifestyle changes in these patients.
“By shining a spotlight on this evidence, we hope to raise awareness among healthcare stakeholders and policymakers on the need for new treatment access and utilization policies that reflect current evidence-based conclusions on obesity,” said Alfredo Penzo-Mendez, ECRI’s Scientific Quality Manager.
Report Findings
Key takeaways from ECRI’s clinical evidence research include:
- GLP-1 RAs are effective to achieve additional, clinically significant weight loss in adolescents and adults with obesity or overweight, as indicated by FDA-approved labeling, and who are committed to achieving weight loss through lifestyle changes such as diet and exercise.
- GLP-1 RAs are intended only as an adjunct to lifestyle modification for weight loss. Intensive behavioral therapy consisting of recommendations on diet—reducing caloric intake by 500 calories per day—and physical activity—a goal of 150 minutes per week of moderate-intensity exercise—is the gold standard lifestyle intervention for weight loss.
- People can benefit from taking GLP-1 RAs at doses below the maximum and should aim for the highest dose they can tolerate. However, if the user does not experience substantial weight loss on this dose after six months, they should stop taking GLP-1 RAs.
- Regaining weight is likely after discontinuing GLP-1 RA therapy; therefore, the drugs are intended for chronic use.
- Mild and transient side effects when treatment starts—e.g., nausea, vomiting, constipation, diarrhea, headaches—can be expected. Rare but serious side effects that warrant monitoring and patient education include pancreatitis, gastroparesis, bowel obstruction, and cholestasis.
Proceed with Caution
Although weight-loss drugs have become very popular, they may not be reaching the patients who would benefit most. Because of the heightened interest in GLP-1 RAs, their use outside the limits supported by clinical evidence may put people at risk and cause undue financial burden. Unsustainable GLP-1 RA use may also cause social trends to reverse, resulting in frustration about barriers to access, unrealistic expectations, and overemphasizing rare side effects.
Counterfeit Medications
Due to shortages of weight-loss medications, compounding pharmacies have been offering their own GLP-1 RA formulations, which may seem a positive development for addressing the shortages. However, both FDA and America's Poison Centers have reported cases of patients experiencing medication errors and adverse events following the use of compounded semaglutide products, raising serious safety concerns.
Worse, counterfeit semaglutide products have been found in the United States and other countries. The FDA has seized many fake Ozempic 1 mg packages, and testing is being done to identify their contents. Some counterfeit semaglutide products in Australia, Belgium, and Lebanon contained or were suspected to contain insulin. As a result, some patients who got these fake products had low blood sugar and needed hospitalization.
Physician-Patient Interactions
Many patients inquiring about GLP-1 RAs may not be good candidates for these new medications, further demonstrating the need for consultations with physicians who encourage evidence-based treatment. For eligible patients, dispelling misconceptions can help patients stay motivated into making long-lasting lifestyle changes.
“One key reason why the weight-loss effort does not deliver the desired result is that much of it is grounded in inaccurate, outdated, or unproven notions,” Penzo-Mendez said.
Misinformation and social media hype can interfere with care and ultimately endanger individuals wanting to lose weight, making it more important than ever for physicians to provide reliable information sources. A review of the patient’s previous attempts to lose weight may identify reasons for failure and motivate them to attempt evidence-based lifestyle changes, with or without weight-loss drugs.
The Centers for Medicare & Medicaid Services (CMS) promote engagement about weight loss by adopting a patient-centric approach with the 5-A Framework:
- Ask: Determine the optimal timing for discussion
- Assess: Evaluate the patient’s need and priorities
- Advise: Counsel the patient on weight loss benefits and options
- Agree: Make joint decisions on treatment and goals
- Assist: Identify and deliver needed support
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. Providing patients with accessible educational resources may make conversations easier and more effective.
Evidence-based practices ensure sustainable GLP-1 RA use by maximizing health benefits and minimizing risks and costs. Prescribing physicians have a central role to play in ensuring appropriate, effective GLP-1 RA use. ECRI remains committed to assist care providers by providing updated review of available clinical evidence and expert guidance to support patient and care-provider decisions.