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DPP-4 Inhibitors and Combinations Step Therapy with Quantity Limit Program Summary

Policy Number: PH-91139

This program applies to Blue Partner, Commercial, GenPlus, Health Insurance Marketplace, NetResults A series, and SourceRx formularies.

POLICY REVIEW CYCLE

Effective Date

Date of Origin   

07-01-2024           

FDA LABELED INDICATIONS AND DOSAGE

Agent(s)

FDA Indication(s)

Notes

Ref#

Janumet®

(sitagliptin/metformin)

Tablet

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Limitations of use:

  • Should not be used in patients with type 1 diabetes. 
  • Has not been studied in patients with a history of pancreatitis

5

Janumet® XR

(sitagliptin-metformin HCl Tab ER)

Tablet

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Limitations of use:

  • Should not be used in patients with type 1 diabetes.
  • Has not been studied in patients with a history of pancreatitis

6

Januvia®

(sitagliptin)

Tablet

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Limitations of use:

  • Should not be used in patients with type 1 diabetes. 
  • Has not been studied in patients with a history of pancreatitis.

1

Jentadueto®

(linagliptin/metformin)

Tablet

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Limitations of use:

  • Should not be used in patients with type 1 diabetes 
  • Has not been studied in patients with a history of pancreatitis

7

Jentadueto XR®

(linagliptin/metformin ER)

Tablet

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Limitations of use:

  • Should not be used in patients with type 1 diabetes 
  • Has not been studied in patients with a history of pancreatitis

8

Kazano™, Alogliptin/metformin

Tablet

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Limitations of use:

  • Should not be used in patients with type 1 diabetes mellitus

10

Kombiglyze™ XR

(saxagliptin/metformin)*

Tablet

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both saxagliptin and metformin is appropriate

Limitations of use:

  • Not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis

*- generic available

9

Nesina®, Alogliptin

Tablet

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Limitations of use:

  • Should not be used in patients with type 1 diabetes mellitus 

2

Onglyza®

(saxagliptin)*

Tablet

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Limitations of use:

  • Not used for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis

*-generic available

3

Oseni®, Alogliptin/pioglitazone

Tablet

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus 

Limitations of use:

  • Should not be used in patients with type 1 diabetes

11

Tradjenta®

(linagliptin)

Tablet

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Limitations of use:

  • Should not be used in patients with type 1 diabetes, as it would not be effective in these settings
  • Has not been studied in patients with a history of pancreatitis

4

Zituvio™

(sitagliptin)

Tablet

Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

Limitations of Use:

  • Zituvio is not recommended in patients with type 1 diabetes mellitus
  • Zituvio has not been studied in patients with a history of pancreatitis

14

See package insert for FDA prescribing information:  https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Diabetes

The American Diabetes Association (ADA) states that first-line therapy depends on comorbidities, patient-centered treatment factors, and management needs and generally includes metformin and comprehensive lifestyle modification. Because type 2 diabetes is a progressive disease in many patients, maintenance of glycemic targets with monotherapy is often possible for only a few years, after which combination therapy is necessary. Traditional recommendations have been to use stepwise addition of medications to metformin to maintain A1C at target.(12,13)

Metformin is effective and safe, is inexpensive, and may reduce risk of cardiovascular events and death. Metformin is available in an immediate-release form for twice-daily dosing or as an extended-release form that can be given once daily. Compared with sulfonylureas, metformin as first-line therapy has beneficial effects on A1C, weight, and cardiovascular mortality.(13)

Safety

Janumet, Jentadueto, Jentadueto XR, Kazano, and Kombiglyze XR carry a black box warning for lactic acidosis:(7-10)

  • Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin associated lactic acidosis was characterized by elevated blood lactate levels (greater than 5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally greater than 5 mcg/ml
  • Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
  • Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high-risk groups are provided in the full prescribing information
  • If metformin-associated lactic acidosis is suspected, immediately discontinue the medication and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

Oseni carries a black box warning for congestive heart failure:(11)

  • Thiazolidinediones, including pioglitazone, cause or exacerbate congestive heart failure in some patients.
  • After initiation of Oseni and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea and/or edema). If heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of pioglitazone in Oseni must be considered.
  • Oseni is not recommended in patients with symptomatic heart failure. Initiation of Oseni in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated.

Janumet, Janumet XR, and Kombiglyze XR have the following contraindications:(5,6,9)

  • Severe renal impairment: (eGFR below 30 mL/min/1.73 m^2).
  • Metabolic acidosis, including diabetic ketoacidosis.
  • History of a serious hypersensitivity reaction (e.g., anaphylaxis, angioedema, exfoliative skin conditions) to the active ingredients, metformin, or any excipients.

Jentadueto, Jentadueto XR, and Kazano have the following contraindications:(7,8,10)

  • Severe renal impairment (eGFR below 30 mL/min/1.73 m^2).
  • Metabolic acidosis, including diabetic ketoacidosis.
  • Hypersensitivity to the active ingredients or any of the excipients. 

Januvia, Nesina, Onglyza, and Tradjenta have the following contraindication:(1-4)

  • History of serious hypersensitivity to the active ingredient or any of the excipients. 

Oseni has the following contraindication:(11)

  • Serious hypersensitivity reaction to alogliptin or pioglitazone, components of Oseni, or any of the excipients.
  • Do not initiate Oseni in patients with established NYHA Class III or IV heart failure. 

Zituvio has the following contraindication:(14)

  • History of a serious hypersensitivity reaction to sitagliptin or any of the excipients in Zituvio, such as anaphylaxis or angioedema.

REFERENCES

Number

Reference

1

Januvia prescribing information. Merck & Co., Inc. July 2022.

2

Nesina prescribing information. Takeda Pharmaceuticals America, Inc. July 2023.

3

Onglyza prescribing information. Astra Zeneca. October 2019.

4

Tradjenta prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. June 2023.

5

Janumet prescribing information. Merck & Co., Inc. July 2022.

6

Janumet XR prescribing information. Merck & Co., Inc. July 2022.

7

Jentadueto prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. June 2023.

8

Jentadueto XR prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. June 2023. 

9

Kombiglyze XR prescribing information. Bristol-Meyers Squibb Company/AstraZeneca Pharmaceuticals LP. October 2019.

10

Kazano prescribing information. Takeda Pharmaceuticals America, Inc. July 2023.

11

Oseni prescribing information. Takeda Pharmaceuticals America, Inc. March 2022.

12

American Diabetes Association. Standards of Medical Care in Diabetes-2022. Available at https://diabetesjournals.org/care/issue/45/Supplement_1.

13

Nuha A. ElSayed, et. al, American Diabetes Association, 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2023. Diabetes Care 1 January 2023; 46 (Supplement_1): S140–S157. https://doi.org/10.2337/dc23-S009.

14

Zituvio prescribing information. Zydus Pharmaceuticals (USA) Inc. October 2023.

POLICY AGENT SUMMARY STEP THERAPY

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Targeted MSC

Available MSC

Final Age Limit

Preferred Status

1-Step Through Preferred

Jentadueto ; Jentadueto xr

linagliptin-metformin hcl tab  ; linagliptin-metformin hcl tab er

2.5-1000 MG ; 2.5-500 MG ; 2.5-850 MG ; 5-1000 MG

M ; N ; O

N

Kazano

alogliptin-metformin hcl tab

12.5-1000 MG ; 12.5-500 MG

M ; N ; O

M ; N

Kombiglyze xr

saxagliptin-metformin hcl tab er

2.5-1000 MG ; 5-1000 MG ; 5-500 MG

M ; N ; O

O ; Y

Nesina

alogliptin benzoate tab

12.5 MG ; 25 MG ; 6.25 MG

M ; N ; O

M ; N

Onglyza

saxagliptin hcl tab

2.5 MG ; 5 MG

M ; N ; O

O ; Y

Oseni

alogliptin-pioglitazone tab

12.5-15 MG ; 12.5-30 MG ; 12.5-45 MG ; 25-15 MG ; 25-30 MG ; 25-45 MG

M ; N ; O

M ; N

Tradjenta

linagliptin tab

5 MG

M ; N ; O

N

Zituvio

sitagliptin tab

100 MG ; 25 MG ; 50 MG

M ; N ; O

N

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

QL Amount

Dose Form

Day Supply

Duration

Addtl QL Info

Allowed Exceptions

Targeted NDCs When Exclusions Exist

Janumet

sitagliptin-metformin hcl tab

50-1000 MG ; 50-500 MG

60

Tablets

30

DAYS

Janumet xr

Sitagliptin-Metformin HCl Tab ER 24HR 100-1000 MG

100-1000 MG

30

Tablets

30

DAYS

Janumet xr

Sitagliptin-Metformin HCl Tab ER 24HR 50-1000 MG

50-1000 MG

60

Tablets

30

DAYS

Janumet xr

Sitagliptin-Metformin HCl Tab ER 24HR 50-500 MG

50-500 MG

30

Tablets

30

DAYS

Januvia

sitagliptin phosphate tab

100 MG ; 25 MG ; 50 MG

30

Tablets

30

DAYS

Jentadueto

linagliptin-metformin hcl tab

2.5-1000 MG ; 2.5-500 MG ; 2.5-850 MG

60

Tablets

30

DAYS

Jentadueto xr

Linagliptin-Metformin HCl Tab ER 24HR 2.5-1000 MG

2.5-1000 MG

60

Tablets

30

DAYS

Jentadueto xr

Linagliptin-Metformin HCl Tab ER 24HR 5-1000 MG

5-1000 MG

30

Tablets

30

DAYS

Kazano

alogliptin-metformin hcl tab

12.5-1000 MG ; 12.5-500 MG

60

Tablets

30

DAYS

Kombiglyze xr

Saxagliptin-Metformin HCl Tab ER 24HR 2.5-1000 MG

2.5-1000 MG

60

Tablets

30

DAYS

Kombiglyze xr

Saxagliptin-Metformin HCl Tab ER 24HR 5-1000 MG

5-1000 MG

30

Tablets

30

DAYS

Kombiglyze xr

Saxagliptin-Metformin HCl Tab ER 24HR 5-500 MG

5-500 MG

30

Tablets

30

DAYS

Nesina

alogliptin benzoate tab

12.5 MG ; 25 MG ; 6.25 MG

30

Tablets

30

DAYS

Onglyza

saxagliptin hcl tab

2.5 MG ; 5 MG

30

Tablets

30

DAYS

Oseni

alogliptin-pioglitazone tab

12.5-15 MG ; 12.5-30 MG ; 12.5-45 MG ; 25-15 MG ; 25-30 MG ; 25-45 MG

30

Tablets

30

DAYS

Tradjenta

linagliptin tab

5 MG

30

Tablets

30

DAYS

Zituvio

sitagliptin tab

25 MG

30

Tablets

30

DAYS

Zituvio

sitagliptin tab

50 MG

30

Tablets

30

DAYS

Zituvio

sitagliptin tab

100 MG

30

Tablets

30

DAYS

CLIENT SUMMARY – STEP THERAPY

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Client Formulary

Jentadueto ; Jentadueto xr

linagliptin-metformin hcl tab  ; linagliptin-metformin hcl tab er

2.5-1000 MG ; 2.5-500 MG ; 2.5-850 MG ; 5-1000 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Kazano

alogliptin-metformin hcl tab

12.5-1000 MG ; 12.5-500 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Kombiglyze xr

saxagliptin-metformin hcl tab er

2.5-1000 MG ; 5-1000 MG ; 5-500 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Nesina

alogliptin benzoate tab

12.5 MG ; 25 MG ; 6.25 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Onglyza

saxagliptin hcl tab

2.5 MG ; 5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Oseni

alogliptin-pioglitazone tab

12.5-15 MG ; 12.5-30 MG ; 12.5-45 MG ; 25-15 MG ; 25-30 MG ; 25-45 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tradjenta

linagliptin tab

5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Zituvio

sitagliptin tab

100 MG ; 25 MG ; 50 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

CLIENT SUMMARY – QUANTITY LIMITS

Target Brand Agent Name(s)

Target Generic Agent Name(s)

Strength

Client Formulary

Janumet

sitagliptin-metformin hcl tab

50-1000 MG ; 50-500 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Janumet xr

Sitagliptin-Metformin HCl Tab ER 24HR 100-1000 MG

100-1000 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Janumet xr

Sitagliptin-Metformin HCl Tab ER 24HR 50-1000 MG

50-1000 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Janumet xr

Sitagliptin-Metformin HCl Tab ER 24HR 50-500 MG

50-500 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Januvia

sitagliptin phosphate tab

100 MG ; 25 MG ; 50 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Jentadueto

linagliptin-metformin hcl tab

2.5-1000 MG ; 2.5-500 MG ; 2.5-850 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Jentadueto xr

Linagliptin-Metformin HCl Tab ER 24HR 2.5-1000 MG

2.5-1000 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Jentadueto xr

Linagliptin-Metformin HCl Tab ER 24HR 5-1000 MG

5-1000 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Kazano

alogliptin-metformin hcl tab

12.5-1000 MG ; 12.5-500 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Kombiglyze xr

Saxagliptin-Metformin HCl Tab ER 24HR 2.5-1000 MG

2.5-1000 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Kombiglyze xr

Saxagliptin-Metformin HCl Tab ER 24HR 5-1000 MG

5-1000 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Kombiglyze xr

Saxagliptin-Metformin HCl Tab ER 24HR 5-500 MG

5-500 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Nesina

alogliptin benzoate tab

12.5 MG ; 25 MG ; 6.25 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Onglyza

saxagliptin hcl tab

2.5 MG ; 5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Oseni

alogliptin-pioglitazone tab

12.5-15 MG ; 12.5-30 MG ; 12.5-45 MG ; 25-15 MG ; 25-30 MG ; 25-45 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tradjenta

linagliptin tab

5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Zituvio

sitagliptin tab

100 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Zituvio

sitagliptin tab

50 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Zituvio

sitagliptin tab

25 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

STEP THERAPY CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

1-Step Through Preferred

Preferred Agents

Non-preferred Agents

Januvia (sitagliptin)     
Janumet (sitagliptin/metformin)
Janumet XR (sitagliptin/metformin extended-release)

Alogliptin
Alogliptin/metformin
Alogliptin/pioglitazone
Jentadueto (linagliptin/metformin)
Jentadueto XR (linagliptin/metformin ER)
Kazano (alogliptin/metformin)
Kombiglyze XR (saxagliptin/metformin ER)
Nesina (alogliptin)
Onglyza (saxagliptin)
Oseni (alogliptin/pioglitazone)
Tradjenta (linagliptin)
Zituvio (sitagliptin)

Target Agent(s) will be approved when ONE of the following is met:

  1. The patient’s medication history includes use of one or more of the following: Januvia, Janumet, Janumet XR OR
  2. The patient has an intolerance or hypersensitivity to a preferred sitagliptin agent OR
  3. The patient has an FDA labeled contraindication to a preferred sitagliptin agent that is not expected to occur with the requested agent

Length of Approval: 12 months

NOTE: If Quantity Limit also applies, please refer to Quantity Limit criteria.

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:

  1. The requested quantity (dose) does NOT exceed the program quantity limit OR
  2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
    1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
    2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
    3. BOTH of the following:
      1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication

Length of Approval: up to 12 months

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

ALBP _  Commercial _ CSReg _ DPP-4_Inhibitors_and_Combinations_STQL _ProgSum_ 07-01-2024  _  © Copyright Prime Therapeutics LLC. May 2024 All Rights Reserved