(October 24, 2024): Semaglutide, tirzepatide and a slate of other GLP-1 receptor agonist medications have dominated weight loss headlines in recent years. Not surprisingly, many weight loss providers and clinics have refocused their approaches, incorporating these drugs into patient treatment regimens. Unfortunately, the popularity of these drugs has led to a variety of bad practices, ranging from overutilization to poor compounding practices. Insurance companies auditing claims for reimbursement have identified documentation deficiencies, improper coding practices, and incidents of outright fraud. In this article, we discuss the current regulatory and enforcement environment and discuss ways that weight loss providers and clinics can reduce their level of risk.
I. Brief History of GLP-1 Receptor Agonist Medications:
Scientists and medical researchers alike have worked for decades to identify a truly effective, non-surgical, weight loss regimen. In 1995, after learning that the venom of a Gila monster lizard contained hormones that can assist with the regulation of blood sugar, Donald Drucker, M.D., a scientist / endocrinologist at the University of Toronto, obtained one of these lizards to further study the venom. Approximately a decade later, a synthetic version of the identified hormone was developed and approved to treat Type 2 diabetes.[1] This synthetic version of the hormone is now known as a GLP-1 receptor agonist. In April 2005, exenatide (also known by its brand name, “Byetta®”), was the first GLP-1 drug approved by the U.S. Food and Drug Administration (FDA), for the treatment of type 2 diabetes. It was specifically approved for adjunctive glycemic control in type 2 diabetic patients taking metformin.[2]
II. Current Status of FDA-Approved Uses of GLP-1 Receptor Agonist Medications:
Since Byetta® was first approved in 2005, a variety of other GLP-1 medications have been brought to market and have been prescribed for both approved and off-label uses. Since 2010, the following events have taken place:
Overview of GLP-1 Receptor Agonists Related Events
| Year | Drug Approved OR Actions Taken |
Discussion |
|---|---|---|
| 2010 | Liraglutide (Injection, for Subcutaneous Use) (also known by its brand name, Victoza®). |
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| 2014 | Dulaglutide (also known by its brand name, Trulicity®). |
|
| 2016 | Liraglutide (Insulin Degludec and Liraglutide Injection, for Subcutaneous Use) (also known by its brand name, Xultophy®). |
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| 2016 | Lixisenatide (Insulin Glargine and Lixisenatide Injection) (also known by its brand name, Soliqua®). |
|
| 2017 | Semaglutide (Oral) (also known by its brand name, Rybelsus®). |
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| 2017 | Semaglutide (Subcutaneous Injection)(also known by its brand name, Ozempic®). |
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| 2021 | Semaglutide (injection for Subcutaneous Use) (also known by its brand name, Wegovy®). |
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| 2022 | Tirzepatide (Injection, for Subcutaneous Use) (also known by its brand name, Mounjaro®). |
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| 2022 | Semaglutide. On August 23, 2022, the FDA placed semaglutide (also known by its brand name, Wegovy®) on the drug shortage list. |
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| 2022 | Tirzepatide. On December 15, 2022, placed tirzepatide (also known by its brand names Mounjaro® and Zepbound®) on the drug shortage list. |
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| 2023 | Tirzepatide (Injection, for Subcutaneous Use) (also known by its brand name, Zepbound®), |
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| 2023 | Semaglutide. On April 27, 2023, the FDA sent a letter to the National Association Boards of Pharmacy discussing the use of compounded semaglutide products. |
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| 2024 | Semaglutide. Earlier this year, the FDA approved a new indication for the use of semaglutide (under the brand name Wegovy®). |
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| 2024 | Tirzepatide. On October 2, 2024, the FDA announced on its website that it was removing tirzepatide from the drug shortage list. [13] |
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| 2024 | Tirzepatide. On October 7, 2024, the Outsourcing Facilities Association[14] filed a lawsuit[15] against the FDA for its action removing tirzepatide from the drug shortage list. |
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| 2024 | Tirzepatide. On October 11, 2024, in response to the lawsuit filed by the Outsourcing Facilities Association, the FDA announced in a court filing that it would allow pharmacists to continue compounded versions of tirzepatide. (the active ingredient in diabetes and weight loss drugs Mounjaro® and Zepbound®). |
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III. Frequently Asked Questions Regarding Weight Loss Medications:
What Does it Mean for a Medication, Drug, or Medical Device to be “Misbranded”?
Under Section 502 of the Federal Food, Drug, and Cosmetic (FD&C) Act,[16] a drug or device shall be deemed as misbranded if its labeling is false or misleading in any way.[17] The FDA has noted that labeling misbrands a product if:
“Its labeling is false or misleading in any particular;
It is in package form and its label fails to contain the name and place of business of the manufacturer, packer, or distributor and an accurate statement of the quantity of the contents in terms of weight, measure, or numerical count;
Any required wording is not prominently displayed as compared with other wording on the device, or is not clearly stated;
Its label does not bear adequate directions for use including warnings against use in certain pathological conditions or by children where its use may be dangerous in health or against unsafe dosage, or methods, or duration of administration or application;
It is dangerous to health when used in the dosage or manner or with the frequency or duration prescribed, recommended or suggested in the labeling; or
It does not comply with the color additives provisions listed under Section 706 of the FFDCA;
The device's established name (if it has one), its name in an official compendium, or any common or usual name is not prominently printed in type at least half as large as that used for any proprietary name;
The establishment is not registered with FDA as required by Section 510 of the FFDCA and has not listed the device as required by Section 510(j) of the FFDCA or obtained applicable premarket notification clearance as required by Section 510(k) of the FFDCA;
The device is subject to a performance standard and it does not bear the labeling prescribed in that standard;
There is a failure or refusal to comply with any requirement related to notification and other remedies prescribed under Section 518 of the FFDCA, if there is a failure to furnish any materials or information required by, or requested by the Secretary pursuant to, Section 519 of the FFDCA, or if there is a failure to furnish materials or information relating to reports and records required by Section 522 of the FFDCA; or
There is any representation that creates an impression of official approval because of the possession by the firm of an FDA registration number”. [18]
Ensuring compliance with these regulations is crucial for the safe and effective use of FDA approved medications.
Why Does it Matter if a Medication has been Placed on the Drug Shortage List?
Under §506c. of the FD&C Act, a “drug shortage” means “a period of time when the demand or projected demand for the drug within the United States exceeds the supply of the drug”.[19] Generally, when an FDA approved drug is placed on the FDA’s drug shortage list, some Federal restrictions are relaxed. As the FDA notes:
“Section 503A of the FD&C Act restricts compounded drugs that are essentially copies of commercially available drugs, but certain amounts are permissible under the law as long as the compounding is not done “regularly or in inordinate amounts”.
A drug is not considered to be commercially available if it is on FDA’s drug shortages list and limitations on compounding are lifted in these circumstances.
All other conditions of section 503A must be met, including compounding based on a valid prescription for an individual patient”.
Can GLP-1 Agonist Medications be Dispensed by an Unlicensed Individual?
Prescription drugs, as defined in 21 C.F.R. 205.3(e) include “any human drug required by Federal law or regulation to be dispensed only by a prescription, including finished dosage forms and active ingredients subject to section 503(b) of the Federal Food, Drug, and Cosmetic Act”.[20] Unlicensed individuals do not have prescriptive authority and therefore cannot prescribe semaglutide, tirzepatide or other GLP-1 receptor agonist medications. Moreover, prescription drugs can only be safely used at the direction, and under the supervision, of a licensed practitioner.
Are there Problems with Prescribing Compounded Versions of Semaglutide or Tirzepatide?
As an initial matter, it is important to outline the nature of “compounding.” As the FDA notes
“Compounding is generally a practice in which a licensed pharmacist, a licensed physician, or, in the case of an outsourcing facility, a person under the supervision of a licensed pharmacist, combines, mixes or alters ingredients of a drug to create a medication tailored to the needs of an individual patient".[21]
The FDA does not approve compounded drugs. Therefore, the agency recommends that compounded drugs should only be used when a patient’s medical needs cannot be met by an FDA-approved drug. In recent years, the FDA has identified multiple safety concerns with various compounded versions of semaglutide. Perhaps more importantly both compounding facilities, distributors, and prescribing providers must keep in mind that pharmaceutical companies owning the patents for branded versions of semaglutide and tirzepatide have been increasingly aggressive in seeking damages against parties alleged to have violated their patent and intellectual property.
Can a Physician Prescribe GLP-1 Receptor Agonist Medications via Telehealth?
Unfortunately, the answer to this question will vary from state to state. Before prescribing GLP-1 receptor agonist medications through telehealth, it is important that a provider review both their state telehealth regulations AND any state restrictions on the prescription of GLP-1 drugs and other weight loss medications.
Can Semaglutide and / or Tirzepatide be Prescribed for Off-Label Uses?
While both semaglutide and tirzepatide are FDA-approved medications, they are only approved for specific uses. For example, semaglutide is ONLY approved indication for “chronic weight management in adults with obesity or overweight with at least one weight-related condition (such as high blood pressure, type 2 diabetes, or high cholesterol), for use in addition to a reduced calorie diet and increased physical activity”. [22] Nevertheless, compounded semaglutide has been prescribed by providers around the country solely for the treatment of obesity and weight management, in an unapproved, off-label fashion.
IV. Federal, State, and Private Payor Audits of Semaglutide and GLP-1 Medication Claims:
In recent years, both Federal and State audits and investigations of GLP-1 medications and the related medical claims submitted to payors have greatly expanded. Depending on the facts, prescribing providers may be subject to audits and investigations by Medicare, Medicaid, State Medical Boards, private payors, and law enforcement.
Private Payor Audits of GLP-1 Medication Claims.
Not surprisingly, most private payors will not cover semaglutide or other GLP-1 medications if the primary purpose of the medication is weight loss. In support of their non-coverage decision, many will point out that weight loss alone is an off-label use of semaglutide. In contrast, if the primary purpose of the medication is to treat type 2 diabetes, coverage is much more likely.
Notably, the National Health Care Anti-Fraud Association, the nation’s leading organization focusing on private payor health care fraud, is keenly aware of the coverage and payment risks presented by GLP-1 receptor agonist medications. At is upcoming November 2024 annual conference, one of the scheduled presentations is titled “GLP-1's Misuse: Addressing Health Plan’s Responsibility for Patient Safety,” [23] and will be examining instances where medications were prescribed for non-covered diagnoses.
Medicare Audits of GLP-1 Receptor Agonist Claims.
Medicare currently covers a limited number of obesity-related services (e.g. bariatric surgery). Nevertheless, at this time, Medicare is prohibited by law from covering medications for weight management.[24] GLP-1 medications may qualify for Medicare coverage if it is medically necessary to treat non-obesity-based, FDA-approved conditions such as type 2 diabetes.
It is important to keep in mind that neither National Coverage Determination (NCD) nor Local Coverage Determination (LCD) guidance covering the coverage and payment of GLP-1 medication claims has been issued by CMS and its contractors. Nevertheless, that does not mean that GLP-1 claims have avoided payor scrutiny. Medicare Administrative Contractors (MACs) and Unified Program Integrity Contractors (UPICs) are actively conducting administrative audits of weight loss-related services and claims.
Warning Letters Issued to Suppliers by the FDA.
Whenever the FDA identifies significant potential violations FD&C statutory and / or regulatory provisions, the agency will send notification of the alleged violation(s) to the targeted company or individual. This notification is referred to as a “Warning Letter”. The FDA’s Warning Letter typically sets out the agency’s concerns and sets a timeframe for receiving a response from the company or individual. In recent years, a number of companies engaged in the manufacture or marketing of compounded semaglutide and / or tirzepatide products have been sent Warning Letters from the FDA. Two examples of Warning Letters sent to companies are listed below:
- Warning Letter -- Misbranded and Unapproved New Drugs. In September 2024, the FDA sent a Warning Letter to the operators of a website advising the operators that misbranded and unapproved new drugs were being marketed for introduction into interstate commerce in violation of Sections 301(a), 301(d), 301(k), 503(b), and 505(a) of the FD&C Act. (Also see 21 U.S.C. §§ 331(a), 331(d), 331(k), 353(b), and 355(a). The FDA noted that the specific misbranded and unapproved being introduced into interstate commerce were semaglutide and tirzepatide drug products. The FDA outlined a number of steps that the company must take to address the violations noted.
- Warning Letter -- Misbranded and Unapproved New Drugs. In February 2024, the FDA sent a Warning Letter to the operators of a website offering semaglutide, tirzepatide, and thymalin products for sale in the United States. Even though the company’s product labeling noted that the products being sold were “research chemicals only” and were “not for human consumption,” the FDA stated that evidence from the website established that these drug products were in fact, intended for human consumption. As such, the products constituted misbranded drugs that were introduced or delivered for introduction into interstate commerce in violation of section 301(a) of the FD&C Act, 21 U.S.C. 331(a). Moreover, the products at issue had not been approved by the FDA and had not been found to be safe and effective. The FDA notified the operators of the website that the failure to address the agency’s concerns may result in legal action.
V. State Medical Board Guidance on the Prescribing of Weight Loss Medications:
Prescribers of both brand name weight loss medications and compounded versions of these medications must ensure that all applicable state licensure obligations are fully met. Positions taken by State Medical Boards in this respect have varied from state to state. For example:
- Mississippi. Mississippi is one of the few states to have disciplined a physician licensee in connection with their GLP-1 prescribing practices. In May 2022, the Mississippi State Board of Medical Licensure received a complaint from a physician alleging that another Mississippi licensee was prescribing Ozempic® by telehealth with no audio or video contact with the patient. Additionally, the prescribing licensee allegedly failed to advise the patient of the possible side effects of using Ozempic®. After conducting a hearing in May 2023, the physician licensee was suspended for three months but the suspension was immediately stayed.
On or about August 29, 2023, the Mississippi State Board of Medical Licensure issued guidance to all physician licensees that they must cease prescribing compounded medications for weight loss. Notably, this occurred long before the FDA removed semaglutide and tirzepatide from the drug shortage list. In support of its position, the Mississippi State Board of Licensure wrote:“Ozempic®, Wegovy®, Mounjaro™ and similar medications are already becoming important tools for treating and managing Type 2 Diabetes and obesity. However, the use of unproven and potentially unsafe compound versions of these patented medications cannot be condoned by the Board under current circumstances”.
In light of this guidance, a Mississippi licensed physician found to violate these restrictions may be subject to disciplinary actions by the Mississippi State Board of Licensure.
- Florida. Notably, the Florida Board of Medicine has a long history of weighing in on the standards that licensees must follow when prescribing obesity drugs.[25] For example, Florida law restricts the prescribing of weight loss medications unless a patient meets certain body mass index (BMI) requirements, informed consent is fully documented and regular follow-ups with the patient are conducted.
- Alabama. In contrast to the more restrictive positions taken by several other states, the Alabama Board of Medical Examiners adopted a more cautionary approach[26] when prescribing or dispensing compounded versions of semaglutide. More specifically, the Board noted that:
“Some unscrupulous healthcare practitioners are using inappropriate personnel to evaluate patients and charging an exorbitant fee for the evaluation. Proper histories, physicals, and confirmatory testing are not performed. Prescriptions or dispensed compounded medications are provided without the patient having seen an appropriate healthcare practitioner. Medications continue to be provided without follow-up exams or testing. . . Other dishonest schemes have been identified; for example, out-of-state pharmacies may be soliciting doctors to prescribe compounded semaglutide to receive a kickback on every prescription.”
VI. Criminal Prosecutions Involving Semaglutide:
While criminal prosecutions of GLP-1 related wrongdoing have been infrequent, audits and investigations of these medications by private payors and State Medical Boards have steadily increased over the last year. Depending on the facts, violations can lead to criminal liability. One example of a recent criminal case brought by Federal prosecutors is discussed below:
New York. Earlier this year, the government announced that it had arrested an individual who was allegedly in receipt of “misbranded drugs in interstate commerce”. More specifically, the defendant allegedly obtained weight loss drugs (such as semaglutide) from sources in Central and South America. None of the weight loss drugs obtained from these sources was approved by the FDA for sale and dispensing in the United States. Notably, all of the labeling on the medication vials sold to a government undercover agent was in Spanish, in violation of FDA’s labeling regulations.The government further contends that the defendant, an unlicensed individual, marketed these weight loss medications through social media (such as TikTok) and dispensed these drugs to individuals without a proper prescription (the defendant did not have prescriptive authority). It was also noted by the government that at least one of the medication vials sold by the defendant tested positive for “mycobacterium abscessus, a species of rapidly growing, multidrug-resistant, nontuberculous mycobacteria”.
VII. Semaglutide Audits / Tirzepatide Audits are on the Rise:
Should you receive notice of an audit or investigation of semaglutide or other GLP-1 claims, we recommend that you call a health law attorney who is experienced in handling these types of cases. Liles Parker attorneys have extensive experience representing health care providers and their practices in administrative, civil, and criminal health care cases. Are your prescribing practices the subject of a semaglutide audit by the government or private payors? Have payors initiated a tiezepatide audit? If so, give us a call.
For a complimentary consultation regarding your case, please give us a call at 1 (800) 475-1906.
Ashley Morgan is a Partner at Liles Parker. She has extensive experience working in health law. Ashley is licensed to practice law in multiple states around the country. Additionally, she holds certifications as a Certified Professional Coder (CPC), a Certified Medical Reimbursement Specialist (CMRS), and a Certified Medical Compliance Officer (CMCO). Her law practice is focused exclusively on health care law, particularly on the appeal of claims denials, provider revocation and suspension actions, and regulatory compliance issues. Ashley has represented a wide variety of providers and suppliers in False Claims Act investigations of Medicare, Medicaid and TRICARE claims, AND private payor claims audits. Are your services or claims being audited or investigated? Call an experienced health law attorney – call Ashley. She can be reached at (202) 298-8750 or by e-mail her at amorgan@lilesparker.com.
- [1] Belluz J. “How a Lizard’s Venom Inspired the Promising Weight Loss Drug Wegovy.” www.vox.com. (July 5, 2021).
- [2] Bond A. “Exenatide (Byetta) as a Novel Treatment Option for Type 2 Diabetes Mellitus”. Proc (Baylor Univ. Med. Center). 2006 Jul;19(3):281-4.
- [3] FDA labeling information for Victoza.
- [4] FDA labeling information for Trulicity.
- [5] FDA labeling information for Xultophy.
- [6] FDA labeling information for Soliqua.
- [7] FDA labeling information for Rybelsus.
- [8] FDA labeling information for Rybelsus.
- [9] FDA labeling information for Wegovy.
- [10] FDA labeling information for Mounjaro
- [11] FDA labeling information for Zepbound.
- [12] FDA Press Release. "FDA Approves First Treatment to Reduce Risk of Serious Health Problems Specifically in Adults with Obesity or Overweight". (March 8, 2024).
- [13] On October 2, 2024, the FDA announced that it was removing tirzepatide from the drug shortage list in its online notice titled "FDA Clarifies Policies for Compounders as National GLP-1 Supply Begins to Stabilize".
- [14] The Outsourcing Facilities Association is the primary trade association representing outsourcing facilities that engage in drug compounding under Federal law.
- [15] A copy of the Complaint can be found here.
- [16] It is worth noting that in its guidance, the FDA refers to the Federal Food, Drug and Cosmetic Act and either the “FD&C Act” or the “FFDC.”
- [17] 21 U.S.C. §352(a)(1).
- [18] See FDA’s online guidance titled “Labeling Requirements – Misbranding".
- [19] See §506C of the Federal Food, Drug and Cosmetic Act.
- [20] See 21.C.F.R. 205.3(e).
- [21] See FDA’s online guidance on "Human Drug Compounding".
- [22] See FDA’s News Release titled "FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014”. (June 4, 2021).
- [23] A copy of NHCAA’s annual conference agenda lists GLP-1 medications as one of the topics to be covered.
- [24] In 2006, as part of the Medicare Prescription Drug, Improvement and Modernization Act (MMA), Congress specifically carved out weight loss treatments from coverage. See Congressional Budget Office’s article titled “How Would Authorizing Medicare to Cover Anti-Obesity Medications Affect the Federal Budget?”
- [25] As early as 1998, the Florida Board of Medicine has regulated weight loss treatment regimens prescribed or performed by licensees.
- [26] Alabama Board of Medical Examiners guidance titled “Concerns with Semaglutide and Other GLP-1 Receptor Agonists”.