Summer 2024

Weighing the Options: Keeping Track of New Obesity Drugs

Fast Focus

Obesity is a common health condition impacting a large portion of the U.S., and when it exists as a comorbidity alongside a work-related injury, it can complicate recovery. Addressing obesity can improve health and claims outcomes, but with several new obesity drugs available and an increase in off-label prescribing of diabetes drugs for obesity, what role will these drugs play in workers’ comp?

Comorbid conditions continue to be a concerning and complicating factor in relation to the medical management of injured workers, with comorbidities being identified as the number one barrier to recovery among a recent survey of 500 industry stakeholders.1 The survey also placed comorbidities as the number two concerning claim complexity, beating out factors such as injury type and undetected fraud, waste and abuse.

Obesity is a known comorbid factor that negatively impacts recovery from injury and is associated with increased workers’ comp costs among non-minor injuries.2 According to NCCI, workers’ comp claims with a comorbid diagnosis have twice the medical costs of similar claims.3

Obesity is a complex disease that occurs when an individual has a body mass index (BMI) – a rough estimate of body fat percentage – of 30 or higher.4 An estimated 42% of Americans are considered obese,5 putting them at risk for several serious diseases and health conditions.

Health Consequences of Obesity

People who are obese are at increased risk of:6

The wide-ranging health impacts of obesity also lead to significant healthcare spending and employee costs.

An average

is spent annually on obesity-related medical care in U.S. adults7

Obesity-related absenteeism costs range between
Workers’ comp claims with an obesity comorbidity are

to be lost time claims3

According to the CDC, factors that can cause or contribute to obesity may include diet and physical activity patterns, sleep routines, genetics, certain medications, and social determinants of health.8

Considering that the causes of obesity can vary, it may be beneficial to employ a multifaceted approach when treating obesity, one that includes diet, exercise, lifestyle changes, and in some cases, prescription medications.

How Obesity Impacts Injured Worker Recovery

Excess fat can cause inflammation that slows the healing process9

Obesity can limit circulation, reducing blood flow to a wound

Pain caused by obesity can increase injury-related pain

Breathing problems secondary to obesity can contraindicate certain medications

High blood pressure and heart conditions secondary to obesity can limit pharmacy options

The Growing Popularity of Newer Obesity Drugs

In the last few years, there have been several new drugs approved for the treatment of obesity, along with an increase in the off-label prescribing of certain diabetes medications for the treatment of obesity. Some of these drugs have even gained serious media attention

For instance, the drug Ozempic® (semaglutide) received endorsements from public figures such as Oprah and Elon Musk, and the TikTok hashtag for Ozempic received over 273 million views; many have attributed this attention to have caused drug shortages for Ozempic.10

Meanwhile, Wegovy® (semaglutide) has seen such successful sales that the manufacturer is struggling to keep up with demand, currently working to double the quantity of lower doses reaching the U.S. by investing $11 billion to expand global production capacity.11

Not only are there shortages of these new drugs, but the demand for them is so high that the FDA published warnings about counterfeit semaglutide products that are available in the U.S. supply chain.12 In another notification, the FDA alerted consumers that compounded semaglutide products marketed for weight loss contained the salt formulation of semaglutide instead of the base formulation, meaning it was a different active ingredient and not proven to be safe or effective.13

While many in the industry find it unlikely that workers’ comp could see a significant amount of these drugs end up in claims, some have argued that there may be precedent, albeit limited, where workers’ comp payers were required to reimburse weight loss programs and bariatric surgery in special cases.14

Currently, the industry is beginning to experience some level of creep, with some of these therapies beginning to trend in workers’ comp prescription drug transaction data compared with 2023.15 And while the overall number of scripts is still very small, the high cost associated with a single prescription can quickly have an impact on spend, making it a drug category to watch.

Additionally, if more group health plans cover these medications, it is worth being informed of the impacts these drugs can have on overall patient health.

Regardless, there is much to learn with these new medications, especially as more are currently in development.

The New Classes of Obesity Drugs

While there are many prescription drugs available for the treatment of obesity, this new wave of medications has been based on certain type 2 diabetes medications that – when combined with diet and exercise – demonstrated significant weight loss.

This led manufacturers to develop new formulations of these diabetes drugs, specifically tailored for the treatment of obesity. Ongoing research is still underway to offer more oral formulations instead of currently available injections.

However, approval and availability are two different things. Due to shortages in FDA-approved therapies specifically indicated for obesity, prescribers in some cases are continuing to prescribe certain diabetes medications off-label for weight loss.

These new diabetes/obesity medications fall into two categories: GLP-1 receptor agonists and SGLT-2 inhibitors.

GLP-1 Agonists

Originally developed to help manage type 2 diabetes by controlling blood sugar levels, glucagon-like peptide 1 (GLP-1) receptor agonists send signals to the brain to create more insulin. This lowers blood sugar and delays digestion and appetite, making individuals feel full for longer.16

The Journal of the American Medical Association (JAMA) found that GLP-1 agonists can help to attain 8-21% weight loss when combined with diet and exercise.17

Common Adverse Reaction in GLP-1 Agonists

While each individual drug within this class offers unique warnings and precautions, several of them come with warnings for thyroid C cell cancers, pancreatitis, and hypoglycemia in conjunction with insulin. Additionally, the following adverse reactions were common across this drug class:

The Different Types of GLP-1 Agonists

OBESITY INDICATION
TYPE 2 DIABETES/OFF-LABEL

Semaglutide

Wegovy® weekly injections – approved for the treatment of obesity

Ozempic® weekly injections – approved for the treatment of type 2 diabetes, but prescribed off-label for the treatment of obesity

Rybelsus® tablets – approved for the treatment of type 2 diabetes, but prescribed off-label for the treatment of obesity

Tirzepatide

Zepbound™ weekly injections – approved for the treatment of obesity

Mounjaro® weekly injections – approved for the treatment of type 2 diabetes, but prescribed off-label for the treatment of obesity

Liraglutide

Saxenda® daily injections – approved for the treatment of obesity

Victoza® daily injections – approved for the treatment of type 2 diabetes

Dulaglutide

Trulicity® weekly injection – approved for the treatment of type 2 diabetes, but prescribed off-label for the treatment of obesity

Exenatide

Byetta® twice daily injections – approved for the treatment of type 2 diabetes, but prescribed off-label for the treatment of obesity

Byudreon BCise® weekly injections – approved for the treatment of type 2 diabetes, but prescribed off-label for the treatment of obesity

GLP-1 Agonists in Development

Retatrutide injectable – Phase 3 trials have begun

Orforglipron tablets – Phase 2 trials were recently completed. Of note, it is believed that if approved, this drug will be easier and more affordable to produce18

Potential Risks for Suicidal Thoughts?

19

The FDA has been evaluating reports of suicidal thoughts or actions in patients treated with GLP-1 agonists, but their preliminary evaluation has not found evidence that these medications cause suicidal thoughts or actions.

The information provided to the FDA was often limited because those events could have been influenced by other factors, and therefore a clear relationship was not demonstrated.

However, because of the small number of suicidal thoughts or actions observed in both people using GLP-1 RAs and in the comparative control groups, the FDA cannot definitively rule out that a small risk may exist; therefore, the FDA is continuing to look into this issue.

SGLT-2 Inhibitors

Sodium glucose cotransporter 2 (SGLT-2) inhibitors were originally developed to help treat type 2 diabetes. SGLT-2 inhibitors lower blood sugar by promoting glucose excretion in the kidneys, removing glucose from the blood via urine, leaving less glucose in the body to turn into fat.20

However, as SGLT-2 inhibitors help burn more calories from the body, this could cause an increased appetite. Monotherapies with SGLT-2 inhibitors are not very effective for weight loss, which is why they are only recommended for weight loss when prescribed with agents that reduce food intake.20

While current clinical research found that GLP-1 agonists are more effective for weight loss than SGLT-2 inhibitors,21 SGLT-2 inhibitors may still be considered popular obesity medications due to ongoing drug shortages, the fact that these medications are available in oral formulations instead of injectables, and due to differences in patient profiles that could make GLP-1 agonists less appropriate for certain individuals.

However, it is important to note that all SGLT-2 inhibitors at this time are only FDA-approved for the treatment of type 2 diabetes in combination with diet and exercise. Any use for the treatment of obesity is considered off-label prescribing.

The Different Types of SGLT-2 Inhibitors

Invokana® (canagliflozin) tablets

Steglatro® (ertugliflozin) tablets

Farxiga® (dapagliflozin) tablets

Jardiance® (empagliflozin) tablets

Brenzavvy™ (bexagliflozin) tablets

Common Adverse Reaction in SGLT-2 Inhibitors

Though each individual drug within this class has its own set of precautions and contraindications, commonly noted adverse events across SGLT-2 inhibitors include:

Keeping Track of Other Obesity Medications

While newer obesity medications may be gaining popularity, it is important to keep track of pre-existing medications, which may see continued use. These drugs may be used by themselves or in combination with newer obesity drugs. And even if newer obesity drugs continue to see prolonged popularity, these pre-existing drugs could still be offered as alternatives in the event of drug shortages or if patient-specific factors rule out the use of GLP-1 agonists or SGLT-2 inhibitors.

Buproprion-naltrexone tablets

A combination antidepressant and opioid antagonist approved for weight loss
  • Contrave

Orlistat capsules

A lipase inhibitor that prevents some of the fat in foods eaten from being absorbed by the intestine, this drug is approved for weight loss
  • Alli®
  • Xenical®

Phentermine-topiramate capsules

A combination anorectic and anticonvulsant, this drug decreases appetite to assist in weight loss
  • Qysmia®
  • Lomaira

Setmelanotide injection

An MC receptor agonist, this drug decreases appetite and increases energy expenditure
  • Imcivree®

Clinical and Safety Considerations for Obesity Drugs

As there is a growing diversity of obesity medications available, the clinical considerations across these drugs also grow more diverse.

Considering the high number of individuals affected by obesity and the rapid-growing popularity of these therapies, it is likely that a portion of workers’ comp patients may be prescribed these drugs outside the scope of their workplace injury – making it helpful to understand how these drugs can impact overall patient and pharmacy management.

As this area of drug development continues to evolve, here are additional considerations as they relate to patient safety.

Increased Popularity May Attract Those Not Suited for Anti-Obesity Drugs

As newer obesity drugs continue to dominate headlines, non-obese individuals may attempt to obtain these drugs. However, these drugs should only be used in obese populations.

Misusing or overusing anti-obesity medications could lead to overdose, low blood sugar, and an increased risk of harmful side effects.

Obesity Drugs Do Not Replace Diet and Exercise

These medications are meant to assist in the loss of weight, not directly cause weight loss. They must be effectively combined with diet and exercise. Failing to do so will reduce efficacy.

Stopping Obesity Drugs Could Lead to Regaining Weight

Obesity drugs are meant to be taken long-term, and if an individual stops taking them, they risk regaining weight. In one study from Diabetes, Obesity, & Metabolism, individuals on these medications lost an average of 17.3% of body weight, but upon quitting the drugs they regained 11.6% of body weight, averaging a net loss of 5.6% overall.22

Dosing Errors May Cause Complications

Many semaglutide products on the market are injectable pens with clear directions on how to set the dial for the correct dose. However, patients may be overzealous and injecting themselves with more semaglutide than recommended.

Poison control centers saw a 1,500% increase in calls related to semaglutide injectable products in 2023, approximately 3,000 calls.23 Many patients have overdosed on semaglutide, resulting in seizures, confusion, passing out, fatigue, weakness, nausea, vomiting, chills, dizziness, and other symptoms.

Planning for Drug Shortages

The sheer popularity of these new anti-obesity drugs has led to drug shortages. If an individual were to receive these obesity medications and had to stop due to ongoing drug shortages, it is important to understand the clinical ramifications – when patients have on-and-off access to these medications, they may experience strong weight fluctuations, which can increase the risk of cardiovascular disease.24

Be Aware of Counterfeit, Compounded, or Other Questionable Products

The high demand for anti-obesity medications has led to many opportunistic individuals trying to cash in on this trend. This, of course, creates questions surrounding the efficacy and safety of medications that a patient may be receiving, raising red flags for pharmacotherapy.

The FDA warned consumers regarding the presence of counterfeit semaglutide products in the drug supply chain, making it important for workers’ comp stakeholders to keep an eye out for fake products that could endanger patients.12

Additionally, the FDA alerted consumers that compounded semaglutide products marketed for weight loss contained the salt formulation of semaglutide instead of the base formulation, meaning it was a different active ingredient and not proven to be safe or effective.13

Finally, individuals may receive anti-obesity medications from medical spas, medical clinics, and weight loss clinics23 – understanding whether or not these products are legitimate, counterfeit, or compounded may be difficult to ascertain.

Keep an Eye Out for Evolving Clinical Research

The pharmacy landscape for anti-obesity drugs continues to evolve, as more new medications are still in research and development. More medications could see approval in the next few years, and it is possible that certain GLP-1 agonists and SGLT-2 inhibitors currently approved for the treatment of type 2 diabetes could gain approval as anti-obesity medications, whether or not they are available in their current dose or a higher dose.

Additionally, currently available anti-obesity drugs could see label changes in the next few years, with additional indications or precautions as clinical research continues.

References

  1. 2024 workers’ comp industry insights survey report. Healthesystems. Feb 2024. https://healthe.systems/survey/compsurvey/2024/
  2. Xuguang T, Su P, Larry Y, et al. Is Obesity associated with adverse workers’ compensation claims outcomes? JOEM. 58(9): p 880-884, September 2016. | DOI: 10.1097/JOM.0000000000000834
  3. Law C, Colon D. Comorbidities in workers’ compensation. NCCI. Oct 2012. https://www.ncci.com/Articles/Pages/II_research-brief-comorbidities-in-workers-compensation-2012.pdf
  4. Defining adult overweight & obesity. CDC. Last reviewed June 3, 2022. https://www.cdc.gov/obesity/basics/adult-defining.html
  5. Adult obesity facts. CDC. Last reviewed May 17, 2022. https://www.cdc.gov/obesity/data/adult.html
  6. Health effects of overweight and obesity. CDC, Last reviewed September 24, 2022. https://www.cdc.gov/healthyweight/effects/index.html
  7. Consequences of obesity. CDC. Last reviewed July 15, 2022. https://www.cdc.gov/obesity/basics/consequences.html
  8. Causes of obesity. CDC. Last reviewed March 21, 2022. https://www.cdc.gov/obesity/basics/causes.html
  9. Rohm TV, Meier DT, Olefsky JM, Donath MY. Inflammation in obesity, diabetes, and related disorders. Immunity. 2022; 55 (1): 31-55. Accessed Feb 2, 2024. https://doi.org/10.1016/j.immuni.2021.12.013
  10. Blum D. What is Ozempic and why is it getting so much attention? New York Times. Nov 22, 2022. https://www.nytimes.com/2022/11/22/well/ozempic-diabetes-weight-loss.html
  11. Hart R. Wegovy: here’s when supply of the weight loss drug could improve this year. Forbes. Feb 2, 2024. https://www.forbes.com/sites/roberthart/2024/02/01/wegovy-supply-heres-when-supply-of-the-weight-loss-drug-could-improve-this-year/?sh=69ccb0d61d64
  12. FDA warns consumers not to use counterfeit Ozempic (semaglutide) found in U.S. drug supply chain. FDA. Dec 21, 2023. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-consumers-not-use-counterfeit-ozempic-semaglutide-found-us-drug-supply-chain
  13. Medications containing semaglutide marketed for type 2 diabetes or weight loss. FDA. Jan 10, 2024. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/medications-containing-semaglutide-marketed-type-2-diabetes-or-weight-loss
  14. Esola L. Comp sector unlikely to buy into diet meds trend. Business Insurance. June 1, 2023. https://www.businessinsurance.com/article/20230601/NEWS08/912357613/Comp-sector-unlikely-to-buy-into-diet-meds-trend
  15. Healthesystems data. February 2024.
  16. Castro MR. GLP-1 agonists: diabetes drugs and weight loss. Mayo Clinic. June 29, 2022. https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/expert-answers/byetta/faq-20057955
  17. Elmaleh-Sachs A, Schwartz JL, Bramante CT, et al. Obesity management in adults: a review. JAMA. 2023;330(20):2000-2015. doi:10.1001/jama.2023.19897
  18. Sidik S. Beyond Ozempic: brand-new obesity drugs will be cheaper and more effective. Nature. June 26, 2023. https://www.nature.com/articles/d41586-023-02092-9
  19. Update on FDA’s ongoing evaluation of reports of suicidal thoughts or actions in patients taking a certain type of medicines approved for type 2 diabetes and obesity. FDA. Jan 11, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/update-fdas-ongoing-evaluation-reports-suicidal-thoughts-or-actions-patients-taking-certain-type
  20. Pereira MJ, Eriksson JW. Emerging Role of SGLT-2 Inhibitors for the Treatment of Obesity. Drugs. 2019 Feb;79(3):219-230. doi: 10.1007/s40265-019-1057-0. PMID: 30701480; PMCID: PMC6394798.
  21. Ma H, Lin YH, Dai LZ, et al. Efficacy and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in overweight/obese patients with or without diabetes mellitus: a systematic review and network meta-analysis. BMJ Open. 2023 Mar 7;13(3):e061807. doi: 10.1136/bmjopen-2022-061807.
  22. Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutdie: the STEP 1 trial extension. Diabetes Obes Metab. 2022 Aug;24(8):1553-1564. doi: 10.1111/dom.14725. Epub 2022 May 19. PMID: 35441470; PMCID: PMC9542252.
  23. Goodman B. Poison centers see nearly 1,500% increase in calls related to injected weight-loss drugs as people accidentally overdose. CNN. Dec 18, 2023. https://www.cnn.com/2023/12/13/health/semaglutide-overdoses-wellness/index.html
  24. Blum D. The Wegovy shortage drags on, leaving patients in limbo. The New York Times. Oct 5, 2023. https://www.nytimes.com/2023/10/05/well/live/wegovy-shortage-ozempic-fda.html

RxInformer

Since 2010, the semi-annual RxInformer clinical journal has been a trusted source of timely information and guidance for workers’ comp payers on how best to manage the care of injured worker claimants and plan for the challenges that lay ahead. The publication is an important part of Healthesystems’ proactive approach to advocating for quality care of injured workers while managing the costs associated with treatment.
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