DPP-4 Inhibitors and Combinations

POLICY NUMBER

L.5.01.418

Glyxambi (empagliflozin/linagliptin)

Janumet (sitagliptin/metformin)

Janumet XR (sitagliptin/metformin extended-release)

Januvia (sitagliptin)

Jentadueto (linagliptin/metformin)

Jentadueto XR (linagliptin/metformin extended-release)

Kazano (alogliptin/metformin)

Kombiglyze XR (saxagliptin/metformin extended-release)

Nesina (alogliptin)

Onglyza (saxagliptin)

Oseni (alogliptin/pioglitazone)

Qtern (dapagliflozin/saxagliptin)

Steglujan (ertugliflozin/sitagliptin)

Tradjenta (linagliptin)

Trijardy XR (empagliflozin/linagliptin/metformin extended-release)

Zituvimet (sitagliptin/metformin)

Zituvimet XR (sitagliptin/metformin extended-release)

Zituvio (sitagliptin)

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

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral diabetes drugs that slow the inactivation of incretin hormones (GLP-1 and GIP). These hormones are involved in the physiologic regulation of glucose homeostasis. DPP-4 inhibitors have generally comparable, modest-glucose lowering effects. Add-on therapy may lead to an A1c reduction of approximately 0.4% to 0.9%, while monotherapy may result in A1c reduction of approximately 0.6% to 0.75%.

DPP-4 inhibitors are not considered as initial therapy for most patients with type 2 diabetes. These medications can be added to metformin, a thiazolidinedione, basal insulin, a sulfonylurea, or a sodium-glucose cotransporter 2 (SGLT2) inhibitor. DPP-4 inhibitors and GLP-1 receptor agonists should not be used concurrently as the combination does not provide additive glucose-lowering effects. Potential advantages of DPP-4 inhibitors include a neutral effect on weight and a relatively low incidence of adverse effects and drug-drug interactions.

POLICY

Effective 10/01/2014, step therapy is required for new start prescriptions for DPP-4 inhibitors when purchased at a pharmacy.

Prior authorization is required.

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

Tradjenta (see Policy Exceptions), Glyxambi, Januvia, Janumet, Janumet XR, Jentadueto, Jentadueto XR, Kazano, Kombiglyze XR, Nesina, Onglyza, and Trijardy XR 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. ONE of the following:

   1. The individual's medication history includes use of one or more of the following antidiabetic agents; metformin, sulfonylurea, metformin/sulfonylurea combination, metformin/ thiazolidinedione (TZD) combination, sulfonylurea/TZD combination, or insulin;

   2. There is documentation that the individual is currently using the requested DPP-4 inhibitor product or the requested DPP-4 inhibitor in another product (single ingredient or combination);

   3. The prescriber states the individual is using the requested DPP-4 inhibitor product or the requested DPP-4 inhibitor in another product (single ingredient or combination) AND is at risk if therapy is changed; OR

   4. The individual has a documented intolerance, FDA labeled contraindication, or hypersensitivity to at least one of the following antidiabetic classes: sulfonylureas, metformin, or insulins.

3. The individual will NOT be using the requested agent in combination with a GLP-1 receptor agonist;

4. The individual does not have any FDA-labeled contraindications to requested agent; AND

5. The dosage prescribed is within the program quantity limits based on approved FDA-labeled dosing.

  The following medications are considered not medically necessary as other formulary options exist for the treatment of type 2 diabetes:

• Oseni

• Qtern

• Steglujan

• Zituvimet

• Zituvimet XR

• Zituvio

POLICY EXCEPTIONS

Tradjenta is currently not covered on BCBSMS closed formularies.

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.

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:

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

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

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

D.  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 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 a 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

08/28/2014: New policy added. Effective 10/01/2014.

08/26/2015: Medical policy revised to add ICD-10 codes.

05/26/2016: Policy number L.5.01.418 added. Policy Guidelines updated to add medically necessary definition.

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

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 section updated to add that Qtern and Steglujan are currently not covered on any BCBSMS formularies. Policy statement updated to add Glyxambi as covered with prior authorization when certain criteria are met. Sources updated.

02/05/2019: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Added statement to perform a formulary drug search on the 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. Policy section updated with formatting changes. Policy statements unchanged. Effective 01/01/2019.

06/30/2020: Policy updated to add Janumet (sitagliptin/metformin) as covered when the listed criteria are met. 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.

02/28/2025: Effective 05/01/2025 - Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy updated to add Jentadueto XR (linagliptin/metformin extended-release) and Zituvio (sitagliptin). Policy description updated regarding DPP-4 inhibitors and to remove clinical rationale information. Policy section updated to add that prior authorization is required and that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Policy statement revised to remove Oseni as covered. Revised policy statement to state that Tradjenta (see Policy Exceptions), Glyxambi, Januvia, Janumet, Janumet XR, Jentadueto, Jentadueto XR, Kazano, Kombiglyze XR, Nesina, and Onglyza may be considered medically necessary when ALL of the criteria are met. Medically necessary criteria updated regarding combination therapy, FDA-labeled contraindications, and dose requirements. Added statement that the following medications are considered not medically necessary as other formulary options exist for the treatment of type 2 diabetes: Oseni, Qtern, Steglujan, and Zituvio. Policy Exceptions updated to state that Tradjenta is currently not covered on BCBSMS closed formularies. Removed statement that Step therapy for DPP-4 inhibitors is not required for FEP members. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and to add information regarding medication intolerance. Sources updated. Policy update effective 05/01/2025.

06/10/2025: Policy updated to add Zituvimet (sitagliptin/metformin) and Zituvimet XR (sitagliptin/metformin extended-release). Policy section updated to add Zituvimet and Zituvimet XR as not medically necessary as other formulary options exist for the treatment of type 2 diabetes. Policy Guidelines updated to change "Medically Necessary" to "medical necessity." Sources updated.

12/02/2025: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy description updated regarding DPP-4 inhibitors and GLP-1 receptor agonists. Policy statement updated to add Trijardy XR as medically necessary when the listed criteria are met. Sources updated.

SOURCE(S)

1. American Diabetes Association Professional Practice Committee; Introduction and Methodology: Standards of Care in Diabetes—2024. Diabetes Care 1 January 2024; 47 (Supplement_1): S1–S4. https://doi.org/10.2337/dc24-SINT

2. Glyxambi prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. June 2024. Last accessed September 2025.

3. Janumet prescribing information. Merck Sharp & Dohme LLC. March 2025. Last accessed September 2025.

4. Janumet XR prescribing information. Merck Sharp & Dohme LLC. March 2025. Last accessed September 2025.

5. Januvia prescribing information. Merck Sharp & Dohme LLC. November 2024. Last accessed September 2025.

6. Jentadueto prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. June 2024. Last accessed September 2025.

7. Jentadueto XR prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. May 2024. Last accessed September 2025.

8. Kazano prescribing information. Takeda Pharmaceuticals America, Inc. May 2025. Last accessed September 2025.

9. Kombiglyze XR prescribing information. AstraZeneca Pharmaceuticals LP. August 2025. Last accessed September 2025.

10. Nesina prescribing information. Takeda Pharmaceuticals America, Inc. February 2025 Last accessed September 2025.

11. Onglyza prescribing information. AstraZeneca Pharmaceuticals LP. October 2024. Last accessed September 2025.

12. Oseni prescribing information. Takeda Pharmaceuticals America, Inc. February 2025. Last accessed September 2025.

13. Qtern prescribing information. AstraZeneca Pharmaceuticals LP. November 2024. Last accessed September 2025.

14. Samson, Susan L. et al. American Association of Clinical Endocrinology Consensus Statement: Comprehensive Type 2 Diabetes Management Algorithm – 2023 Update. Endocrine Practice, Volume 29, Issue 5, 305 - 340.

15. Steglujan prescribing information. Merck Sharp & Dohme LLC. December 2024. Last accessed September 2025.

16. Tradjenta prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. March 2025. Last accessed September 2025.

17. Trijardy XR prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. June 2024. Last accessed October 2025.

18. Zituvimet prescribing information. Zydus Lifesciences Limited. June 2025. Last accessed September 2025.

19. Zituvimet XR prescribing information. Zydus Pharmaceuticals USA Inc. July 2024. Last accessed September 2025.

20. Zituvio prescribing information. Zydus Pharmaceuticals (USA) Inc. January 2025. Last accessed September 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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