Antiobesity Medications

As of March 2023, the FDA has approved the use of five medications for long-term treatment of overweight and obesity.

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February 26, 2024

For employers seeking to align their weight management strategy with the latest evidence, this resource offers recommendations on creating a comprehensive benefits package to treat obesity, including behavior-based interventions and pharmacological and surgical treatment.

What Are Antiobesity Medications?

As of January 2024, the FDA has approved the use of six medications for long-term treatment of overweight and obesity:

  • Orlistat* (Xenical®);
  • Liraglutide (Saxenda®);
  • Phentermine-topiramate (Qsymia®);
  • Naltrexone HCl/bupropion HCl (Contrave®);
  • Semaglutide (Wegovy®); and
  • Tirzepatide (Zepbound®).

In addition to the medications listed above, the FDA has approved two medications, Myalept® and Imcivree®, for individuals with rare obesity syndromes. Furthermore, the FDA has approved weight loss medications for short-term use only (less than 12 weeks). These include the generic drugs phentermine and diethylpropion.1

There are also numerous FDA-approved medications that may be prescribed off-label to treat overweight or obesity because they have demonstrated weight loss as a side effect. These include but aren’t limited to medications to treat diabetes -including GLP-1s like Mounjaro® and Ozempic®- as well as depression and seizures.

*A lower dose of the medication (60 mg) is available over the counter under the brand name Alli®

Which Antiobesity Medications are GLP-1s? 

GLP-1 agonists (GLP-1s) are a class of drugs that have been used to treat type 2 diabetes for years. Three have been approved to treat people with overweight or obesity without diabetes: Saxenda®, Wegovy® and Zepbound® (a medication that acts as both a dual GLP-1 and GIP receptor agonist). Several more are in the drug development pipeline, including oral forms of GLP-1s.2

How are GLP-1s Different from Other Antiobesity Medications? 

GLP-1s are categorically different from prior antiobesity medications. They help patients achieve notably higher weight loss than other available antiobesity medications, which is achieved through appetite suppression, improved blood sugar management and slowed stomach emptying.3,4 There is also evidence to indicate that GLP-1s influence reward pathways.5 As a result, scientists are exploring GLP-1s' potential to address reward system-related disorders like drug, alcohol and nicotine use.5,6 Data released in November 2023 also indicate positive effects beyond weight loss to also include cardiometabolic outcomes, leading some researchers to study its potential for the primary and secondary prevention of cardiovascular disease in specific populations.7-10,11

For Whom are Antiobesity Medications Indicated?

The six antiobesity medications approved for long-term use are indicated for adults with a BMI ≥30 or BMI ≥27 with a weight-related comorbidity. Myalept® and Imcivree® are indicated for individuals with rare obesity syndromes.12 Four medications (Orlistat®, Saxenda®, Qsymia® and Wegovy®) have also been approved for use in adolescents with overweight or obesity.13-16 All antiobesity medications are intended to be used as an adjunct to lifestyle interventions. 

Why Should Employers Consider Providing Coverage for Antiobesity Medications?

Many people with overweight and obesity cannot achieve clinically significant weight loss through lifestyle interventions alone. That’s because those with overweight and obesity are grappling with their own biology as they try to lose weight and keep it off; as people lose weight, appetite increases and metabolism slows, which is the body’s way of re-establishing its so-called ‘setpoint’ (the amount of fat our brain believes is necessary to sustain proper functioning).17,18

For those who qualify, antiobesity medications can be a useful tool alongside intensive behavioral interventions to help lose weight and keep it off; clinical trials, along with studies of employees in the real world, show that people with overweight or obesity who take antiobesity medication and engage in behavior change interventions achieve greater weight loss than those who engage in behavior change interventions alone.


What Is the Efficacy of Antiobesity Medications in Adults?

While efficacy varies, clinical trials show that people who take antiobesity medications are more likely to lose at least 5% of their body weight than those who take placebo. Among antiobesity medications, the greatest weight loss is associated with Zepbound®, followed by Wegovy®. According to a physician quoted in The New York Times, “[Zepbound] is now likely the most effective treatment to combat obesity besides bariatric surgery,” with clinical trial results demonstrating 18% average weight loss.19,20  The largest clinical trial of Wegovy® showed that when it was used in conjunction with lifestyle changes, it led to an average 14.9% reduction in body weight after 68 weeks.3

Among FDA-approved antiobesity medications that are not GLP-1s, high-dose phentermine-topiramate (Qsymia®) was associated with the greatest weight loss; at 108 weeks – the longest study of this drug – those who took a higher dose of phentermine-topiramate lost 10.5% of their baseline weight.21

Specific information on the effectiveness of the six FDA-approved antiobesity medications for non-syndromic obesity is included in the Appendix


Beyond clinical trial data, the efficacy of antiobesity medications has been evaluated in an employer population. Results from the study showed greater weight loss among those who received an antiobesity medication and participated in an employer-based weight management program than those who participated in the weight management program alone. Participants who received the antiobesity medication were more likely to lose 5% of their body weight and were more adherent to the weight management program than those who didn’t.22 

Efficacy of Antiobesity Medications in Adolescents

While the efficacy of antiobesity medications in adolescents varies, studies of Orlistat®, Saxenda® and Qsymia® show that BMI decreased among those who took antiobesity medications. Among adolescents who did not take antiobesity medications, BMI either increased or did not change.15,23,24 It is reported that several pharmaceutical companies are starting to explore testing the use of Mounjaro® and Saxenda® in children as young as age 6.25


What Is the Safety Profile of Antiobesity Medications?

Side Effects

As with any drug, there are risks associated with antiobesity medications. Clinical trial data show that side effects vary by medication but include dizziness, headaches, dry mouth, nausea, diarrhea and constipation.26 All antiobesity medications are contraindicated in pregnancy; other contraindications and precautions vary by drug type and age (adolescents vs. adults). In addition, emerging research indicates that individuals using GLP-1s may experience a greater risk of severe digestive issues, including pancreatitis, stomach paralysis and bowel obstructions.27

Beyond physical side effects, as noted above, there is evidence to show that GLP-1s affect reward pathways, with some patients reporting a reduced desire to drink alcohol or use nicotine.28

In addition to the aforementioned side effects, there have been anecdotal reports linking suicidal ideation to use of GLP-1 drugs.29 However, a large analysis of more than 1.8 million patients’ electronic medical records published in January 2024, found no evidence to support an increased link to suicidal ideation among those patients taking semaglutide relative to other treatments for weight loss or diabetes.30 The potential link to adverse events is also being looked into by various regulatory authorities, including the FDA and the European Medicines Agency (EMA).29

Cardiovascular Safety

Beginning in 1997, several medications for weight loss were withdrawn from the market in the U.S. due to serious side effects, including adverse cardiovascular outcomes. Because of this, the FDA now requires approved medications to undergo post-marketing trials to assess cardiovascular effects; these studies are ongoing.31 Thus far, clinical trial data assessing the efficacy of antiobesity medications have demonstrated positive effects on cardiometabolic risk factors (e.g., cholesterol), and few adverse cardiovascular events have been reported.7,32 In fact, recent studies have demonstrated broader cardiometabolic benefits of GLP-1s.33,10 According to the results of the SELECT trial, use of semaglutide (Wegovy®) significantly decreased major adverse cardiovascular events, including non-fatal heart attack and stroke, by 20% among patients with overweight or obesity and cardiovascular disease without diabetes.9

Musculoskeletal Safety

One study suggests there may be some potential clinical benefits when using GLP-1s as therapeutic treatment in the progression as knee osteoarthritis.34

Cancer Risk

In 2020, lorcaserin (Belviq®) was withdrawn after a safety clinical trial showed an increased occurrence of cancer in those taking the drug.35 While some reports suggest an increased risk of pancreatic cancers or pancreatitis with use of GLP-1s, a meta-analysis of the literature found there was no statistically significant difference in pancreatic cancer risk associated with GLP-1s.36 As with other FDA-approved medications, therefore, future studies are needed to assess long-term effects and associated risks of using these medications.

What Is the Utilization of Antiobesity Medications?

Utilization of antiobesity medications has historically been low but has quickly increased in recent years - a trend which is expected to continue due to rising popularity. For example, CVS saw 15% growth in utilization from the third quarter in 2020 to the third quarter of 2021 for antiobesity drugs, with Saxenda® and Wegovy® driving this trend.37 Moreover, across Milliman’s 2023 book of business, weight loss drug utilization increased by 40% from 2021 to 2022 and continued to increase in 2023.38 Another claims analysis quantifying the increase in GLP-1 prescriptions for insured U.S. patients who do not have diabetes found a 2,082% rise in prescriptions from 2019 to 2022.39

Due to increasing utilization, GLP-1s have been in short supply.40 Due to these shortages, Wegovy’s® manufacturer has limited the number of patients who are able to start treatment, and this practice may persist into 2024.41 The continued demand for GLP-1s, coupled with their short supply, has led some patients to seek compounded versions of these medications, which the FDA has advised against due to safety concerns.42 Some are projecting that the approval of Zepbound® in 2023 may ease shortages in the U.S. 

For more information on the factors driving increased utilization of GLP-1s and associated considerations, see Managing Blockbuster GLP-1 Medications: What Employers Need to Know and What They Can Do.

What Factors Influence Antiobesity Medication Utilization? 

Numerous factors impact the utilization of antiobesity medications, including coverage, patient demand, provider prescribing, costs and side effects:

  • Patient demand and provider beliefs: Growing awareness among the public and an increasing number of providers writing prescriptions for GLP-1s are driving growth in utilization; from July 2020 to March 2023, there was a 228% rise in the number of providers prescribing GLP-1s.43 There is also growing awareness and acceptance that obesity is not merely a lifestyle issue but disease caused by multiple factors.44
  • Coverage: Findings from the Business Group’s 2024 Large Employer Health Care Strategy Survey reveal that almost half (49%) of employer respondents provide coverage of GLP-1 drugs for weight loss.45 This is consistent with findings from CVS Caremark, which reports that only about half of its clients cover weight loss medications. Among pharmacy benefit managers (PBMs), CVS Caremark includes Saxenda®, Wegovy® and Qysmia® on its 2023 preferred drug list for antiobesity medications, Optum Rx includes Saxenda®, Wegovy® and Qysmia® on its 2023 select standard formulary and Express Scripts covers Wegovy®, on its 2023 national preferred formulary.46-48 Future coverage of GLP-s is uncertain; a survey of 502 U.S. employers shows that there is an increasing number of employers covering antiobesity medications, including GLP-1 drugs, with coverage predicted to nearly double from 2023 to 2024, while other sources indicate that coverage may be narrowing, as some insurers stop coverage for GLP-1s in light of their skyrocketing utilization.37,49,50
  • Costs: Although GLP-1s and other antiobesity medications have been heralded for their potential to help people with obesity achieve clinically significant weight loss, the high costs of GLP-1s and the chronic nature of their use is presenting significant challenges for employers and patients alike, influencing access, coverage and utilization. The average cash price per month for GLP-1s approved for weight loss in 2023 was about $1,349 for Wegovy® and Saxenda® and $1,059.87 for Zepbound®.51,52 According to analysis by Aon of prescription claims from 500 employers, utilization of weight loss drugs Saxenda®, Wegovy® and Rybelsus®, along with off-label usage of Ozempic for weight loss, increased employer health care costs by more than $300 per worker in 2023. The price of non-GLP antiobesity medications is much lower, at $225 per month for Xenical®, $304 for Contrave® and $134 for Qysmia®.51-56
  • Side effects: There are several well-known side effects of GLP-1s, including nausea, diarrhea, loss of appetite, headaches and back pain.57 Anecdotally, there is evidence to suggest that these side effects may play a role in patient non-adherence to GLP-1s though more research is needed to better understand this.57 An initial study indicated that 68% of patients stopped using GLP-1s within a year, but whether this is due to side effects, medication costs, patient expectations, or a combination of these factors is unknown.58,59

What Should Employers Consider When Assessing and Implementing Coverage for Antiobesity Medications?

  • Do you already include pharmacotherapy in your company’s weight management strategy?

    Check your summary plan description(s) to confirm whether your plan(s) include coverage of antiobesity medications, including GLP-1s for weight loss, as these medications are not standard across PBM formularies. If you currently cover antiobesity medications or wish to in the future, consider including multiple agents on your formulary. For example, in its Federal Employees Health Benefits (FEHB) Program carrier letter, the U.S. Office of Personnel Management (OPM), the chief human resource agency for the federal government, indicated that “carriers must cover at least one anti-obesity drug from the GLP-1 class for weight loss and cover at least two additional oral anti-obesity drug options.”60 Covering multiple agents is important because while employees with overweight or obesity may respond favorably to at least one drug, the response may vary from medication to medication. Furthermore, while GLP-1s can be highly efficacious, other types of antiobesity medications can also help patients achieve clinically significant weight loss.

  • What is the current cost and utilization of off-label prescribing? Work with your partners to determine utilization and costs associated with medications prescribed off label for weight loss, as numerous drugs have been approved by the FDA to treat other conditions (such as type 2 diabetes) and may be used to help patients lose weight. While some of this off-label prescribing may be thoughtful and appropriate, there are other instances where it is not. Clarifying the cost and utilization of off-label use may help organizations that do not currently cover antiobesity medications understand the implications of doing so. It may also help with the decision to implement potential strategies to promote appropriate use.  
  • What type of utilization management tools should be implemented to ensure appropriate use? Ask existing or prospective vendor partners, including virtual weight management programs, about their processes to promote appropriate access and utilization of antiobesity medications, including if they require biometric testing to determine if patients are candidates for pharmacotherapy. Consider implementing step therapy based on efficacy and cost when covering multiple medications.
  • What are the health equity impacts? Even when providing coverage for antiobesity drugs, high out-of-pocket costs may render them unattainable for lower-income individuals. It is important for employers to develop a strategy to address disparities in access to these medications.
  • How are intensive behavioral interventions integrated with antiobesity medications? Promote the use of intensive behavioral interventions alongside pharmacotherapy, as the combination of these programs with antiobesity medications leads to clinically significant weight loss.13,30,31 Some employers pair intensive behavioral interventions and antiobesity medications as part of their on-site services, and many weight management programs now combine the two as part of their care models. As a part of these care models, employers should assess the degree and frequency of patient monitoring and support for the duration of treatment and require appropriate reporting of outcomes to ensure effectiveness.
  • Are your corresponding communications stigma-free? Employers and partners should eliminate stigmatizing language and imagery in all program materials, including evaluating existing and future content for issues like headless images of individuals who have obesity, associations of character or intelligence with body weight, derogatory language or inappropriate humor.

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TABLE OF CONTENTS

  1. What Are Antiobesity Medications?
  2. Which Antiobesity Medications are GLP-1s?
  3. How are GLP-1s Different from Other Antiobesity Medications?
  4. For Whom are Antiobesity Medications Indicated?
  5. What Is the Efficacy of Antiobesity Medications in Adults?
  6. What Is the Safety Profile of Antiobesity Medications?
  7. What Is the Utilization of Antiobesity Medications?
  8. What Factors Influence Antiobesity Medication Utilization?
  9. What Should Employers Consider When Assessing and Implementing Coverage for Antiobesity Medications?