GLP-1 Agonist

POLICY NUMBER

L.5.01.428

Bydureon BCise (exenatide, extended-release injection)

Byetta (exenatide injection)

Mounjaro (tirzepatide injection)

Ozempic (semaglutide injection)

Rybelsus (semaglutide tablets)

Trulicity (dulaglutide injection)

Victoza (liraglutide injection)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that is released, along with glucose-dependent insulinotropic polypeptide (GIP), after ingestion and absorption of glucose, protein, and fat. GLP-1 binds to GLP-1 receptors and stimulates glucose-dependent insulin release from the pancreatic islets. GLP-1 has also been shown to slow gastric emptying, inhibit inappropriate post-meal glucagon release, and reduce food intake. GLP-1 agonist medications are indicated as an adjunct to diet and exercise to improve glycemic control in individuals with type 2 diabetes. GLP-1 agonists are incretin mimetic medications that bind and activate the human GLP-1 receptor. DPP-4 inhibitors increase endogenous GLP-1 via inhibition of DPP-4. GLP-1 agonists should not be combined with DPP-4 inhibitors as there does not appear to be additive effects on glucose lowering.

Bydureon BCise (exenatide extended-release) is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus.

Byetta (exenatide) indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Mounjaro (tirzepatide) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Ozempic (semaglutide) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus, to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease, to reduce the risk of sustained eGFR decline, end-stage kidney disease, and cardiovascular death in adults with type 2 diabetes mellitus and chronic kidney disease.

Rybelsus (semaglutide) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Trulicity (dulaglutide) is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus and to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors.

Victoza (liraglutide) is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus and to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease.

POLICY

Prior authorization is required.

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements.

Mounjaro, Ozempic, Rybelsus, and Trulicity may be considered medically necessary when ALL of the following criteria are met:

1. The individual is being treated as an adjunct to diet and exercise for a diagnosis of type 2 diabetes;

2. The individual’s diagnosis has been confirmed by lab tests (e.g., A1C greater than or equal to 6.5%) (lab test results required);

3. ONE of the following:

   1. The individual's medication history shows recent (within the last 6 months) or current use of metformin;

   2. There is documentation that the individual is currently using the requested medication; OR

   3. The prescribing physician states the individual is using the requested medication and is at risk if therapy is changed;

   4. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to metformin;

4. The individual will NOT be using the requested agent in combination with a DPP-4 containing agent (e.g., Glyxambi, Januvia, Janumet, Jentadueto, Kazano, Kombiglyze, Nesina, Onglyza, Tradjenta) for the requested indication;

5. The individual will NOT be using the requested agent in combination with another GLP-1 receptor agonist agent; AND

6. The individual does NOT have any FDA labeled contraindications to the requested agent.

The following medications are considered not medically necessary as other formulary options exist:

• Byetta (exenatide)

• Bydureon (exenatide)

• Victoza (liraglutide)

POLICY EXCEPTIONS

State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

Rankin County Board of Supervisors Self-Insured Group: Effective 06/16/2025, Zepbound is covered without Prior Authorization. (FID#: 89804 Formulary Name: BCBSMS COMM-CUSTOM RCBOS)

Structural Steel Self-Insured Group: Effective 06/16/2025, all GLP-1 agonist medications are covered without Prior Authorization. (FID#: 89805 Formulary Name: BCBSMS COMM-CUSTOM STEEL) 

Glenn Machine Works Self-Insured Group: Effective 12/01/2025, Wegovy and Zepbound are covered without Prior Authorization. (FID#: 89803 Formulary Name: BCBSMS COMM-CUSTOM GMWCF)

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

1. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

2. appropriate with regard to standards of good medical practice; and

3. not solely for the convenience of the Member, his or her Provider; and

4. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Medication Failure

Medication failure is defined as disease progression at generally accepted doses (for ≥3 months’ use) as appropriate for the disease state being treated. Dosages below the recommended dose for the specific condition being treated and/or experience of common side effects of medication will not be considered medication failure or lack of response for the purpose of this review.

Medication Intolerance

Medication intolerance is defined as the inability to digest, metabolize, or mitigate the expected adverse effects of a prerequisite medication for ≥4 weeks use as evidenced by documented attempted intervention(s) to minimize sensitivity where appropriate (i.e., dose titration, dose reduction, administered with food, administration at different times of day, use of alternative formulation(s) etc.) and claims history. Experience of common side effects of medication will not be considered medication intolerance for the purpose of this review.

BCBSMS determines patient medication trial and adherence by a review of pharmacy claims data over the preceding twelve months. Additional information may be requested on a case-by-case basis to allow for proper review. If member is new to BCBSMS and pharmacy records are needed to confirm medication trials and adherence, it is the responsibility of the member and/or requesting provider to obtain said records and to submit them to BCBSMS upon request. Medical records from the provider that list previously prescribed medications will not be sufficient to show medication trials or adherence.

POLICY HISTORY

11/30/2012: New policy added. Effective 01/01/2013.

08/28/2015: Medical policy revised to add ICD-10 codes.

05/26/2016: Policy number L.5.01.428 added. Investigative definition updated in Policy Guidelines section.

06/13/2016: Approved by Pharmacy & Therapeutics (P&T) Committee.

09/30/2016: Code Reference section updated to add new ICD-10 diagnosis codes E13.37X1 - E13.37X9.

01/01/2017: Policy description revised. In policy section, added statement to perform a formulary drug search on patient's member ID to ensure prescription drug is covered under their benefit plan. Added statement that GLP-1 agonists require step therapy when purchased at a pharmacy. Added statements that Byetta® is not covered on BCBSMS closed formularies, and Bydureon® and Tanzeum™ are not currently covered on any BCBSMS formulary. Policy statement updated to remove Byetta and add Trulicity as covered with prior authorization when certain criteria are met. Policy exceptions updated to change "Byetta/Victoza" to "GLP-1 agonists." Sources section updated.

02/07/2017: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

09/29/2017: Code Reference section updated to add new ICD-10 diagnosis codes E11.10 and E11.11. Effective 10/01/2017.

02/06/2018: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

07/01/2018: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Added drug names to the top of the policy. Policy statement revised to include Byetta® as not covered on any BCBSMS formulary. It previously stated: Byetta® is not covered on BCBSMS closed formularies. Added Ozempic as covered with prior authorization when certain conditions are met. Sources updated.

09/27/2018: Policy updated to make correction: for Bydureon, "enenatide" should be "exenatide."

02/05/2019: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy statement updated to add the following condition for coverage: The patient is being treated as an adjunct to diet and exercise for a diagnosis of type 2 diabetes. Effective 01/01/2019.

04/01/2020: Added Rybelsus as covered with prior authorization when certain conditions are met. Sources updated.

01/01/2021: Added Soliqua (insulin glargine/lixisenatide) and Xultophy (insulin degludec/liraglutide) to the top of the policy. Policy section updated to add the following: 1) Prior authorization is required. 2) The use of samples by a Member will not be considered current or stable therapy for the purposes of Medical Policy review. Policy statement revised to state that Ozempic, Rybelsus, Soliqua, Trulicity, Victoza, and Xultophy may be considered medically necessary when ALL of the listed criteria are met. Added policy statement to state that Byetta (exenatide), Bydureon (exenatide), and Tanzeum (albiglutide) are considered not medically necessary as other formulary options exist. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders." 

06/06/2022: Removed the following Policy Exception statement: Step therapy for GLP-1 agonists is not required for Federal Employee Program (FEP) and State Health Plan members.

11/03/2022: Policy updated to add Mounjaro (tirzepatide) as not medically necessary as other formulary options exist. Sources updated.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

11/27/2023: Policy updated to state that Mounjaro may be considered medically necessary when the specified criteria are met effective 12/01/2023. Added Adlyxin to the not medically necessary policy statement. Removed Soliqua (insulin glargine/lixisenatide) and Xultophy (insulin degludec/liraglutide) from the policy. Sources updated.

01/01/2024: Policy updated to move Victoza (liraglutide) to the not medically necessary policy statement.

06/28/2024: Policy statement updated to revise medically necessary criteria for Mounjaro, Ozempic, Rybelsus, and Trulicity. Added that type 2 diabetes diagnosis must be confirmed by lab tests (e.g., A1C greater than or equal to 6.5%). Also added that the requested GLP-1 agent cannot be used in combination with a DPP-4 containing agent or with another GLP-1 receptor agonist agent. Removed Adlyxin (lixisenatide) and Tanzeum (albiglutide) from the policy. Changed "patient" to "individual" throughout. Policy Guidelines updated to add medication failure definition and remove investigative definition. Sources updated. Effective 07/01/2024.

06/03/2025: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy description updated regarding indications for Glucagon-like peptide-1 (GLP-1), Bydureon BCise (exenatide extended-release), Byetta (exenatide), Mounjaro (tirzepatide), Ozempic (semaglutide), Rybelsus (semaglutide), Trulicity (dulaglutide), and Victoza (liraglutide). Policy statement revised to state that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Medically necessary criteria updated regarding DPP-4 containing agents and contraindications. Policy Guidelines updated regarding medication intolerance. Sources updated.

06/16/2025: Added Self-Insured Group exception.

12/01/2025: Added Self-Insured Group exception. 

SOURCE(S)

1. Byetta prescribing information. AstraZeneca Pharmaceuticals, LP. November 2024. Last accessed March 2025.

2. Bydureon BCise prescribing information. AstraZeneca Pharmaceuticals, LP. November 2024. Last accessed March 2025.

3. Mounjaro prescribing information. Eli Lilly and Company. January 2025. Last accessed March 2025.

4. Ozempic prescribing information. Novo Nordisk. January 2025. Last accessed March 2025.

5. Rybelsus prescribing information. Novo Nordisk. December 2024. Last accessed March 2025.

6. Trulicity prescribing information. Eli Lilly and Company. November 2024. Last accessed March 2025.

7. Victoza prescribing information. Novo Nordisk. February 2025. Last accessed March 2025.

8. American Diabetes Association Professional Practice Committee. 2. Diagnosis and classification of diabetes: Standards of Care in Diabetes—2025. Diabetes Care 2025;48(Suppl. 1):S27–S49.

9. American Diabetes Association Professional Practice Committee. 9. Pharmacologic approaches to glycemic treatment: Standards of Care in Diabetes—2025. Diabetes Care 2025;48(Suppl. 1):S207–S238.

10. American Diabetes Association Professional Practice Committee. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025. Diabetes Care 2025;48(Suppl. 1):S27–S49.

11. Dungan K, DeSantis A. Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus. In: UpToDate, Connor RF (Ed), Wolters Kluwer. https://www.uptodate.com/contents/glucagon-like-peptide-1-based-therapies-for-the-treatment-of-type-2-diabetes-mellitus (Accessed on March 13, 2025.)

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Covered Codes

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