Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors (INVOKANA, INVOKAMET/XR, STEGLATRO, STEGLUROMET, STEGLUJAN, QTERN, BRENZAVVY, INPEFA, brand Dapagliflozin, brand Dapagliflozin-Metformin)

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors (INVOKANA, INVOKAMET/XR, STEGLATRO, STEGLUROMET, STEGLUJAN, QTERN, BRENZAVVY, INPEFA, brand dapagliflozin, brand dapagliflozin, brand dapagliflozin/metformin)

Self-Administration – oral tablets

Diagnosis considered for coverage:

BRENZAVVY (bexagliflozin)

• Type 2 Diabetes: Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
  • Limitations of Use: Brenzavvy is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus.

INVOKAMET (canagliflozin/metformin); INVOKAMET XR (canagliflozin/metformin)

• Type 2 Diabetes: Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• Type 2 diabetes mellitus and established cardiovascular disease (CVD): Canagliflozin is indicated to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease (CVD).
• Type 2 diabetes mellitus and diabetic nephropathy: Canagliflozin is indicated to reduce the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular (CV) death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria greater than 300 mg/day.
  • Limitations of Use: Not recommended in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients.

INVOKANA (canagliflozin)

• Type 2 Diabetes: Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• Type 2 diabetes mellitus and established cardiovascular disease (CVD): Indicated to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease (CVD).
• Type 2 diabetes mellitus and diabetic nephropathy: Indicated to reduce the risk of end-stage kidney disease (ESKD), doubling of serum creatinine, cardiovascular (CV) death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria greater than 300 mg/day.
  • Limitations of use: Invokana is not recommended in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients. Invokana is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 30 mL/min/1.73 m2. Invokana is likely to be ineffective in this setting based upon its mechanism of action.

QTERN (dapagliflozin and saxagliptin)

• Type 2 Diabetes: Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
  • Limitations of Use: Qtern is not recommended for patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients.

SEGLUROMET (ertugliflozin and metformin)

• Type 2 Diabetes: Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
  • Limitations of Use: Not recommended in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients.

STEGLATRO (ertugliflozin)

• Type 2 Diabetes: Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
  • Limitations of use: Steglatro is not recommended in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients.

STEGLUJAN (ertugliflozin and sitagliptin)

• Type 2 Diabetes: Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
  • Limitations of Use: Not recommended in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients Steglujan has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using Steglujan.

INPEFA (sotagliflozin)

• Heart failure or Type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors: Indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with: 1) heart failure, or 2) type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors.

Brand Dapagliflozin (Farxiga ABA) 

• Heart failure, Type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors: Indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with: 1) heart failure, or 2) type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors.

Brand Dapagliflozin/Metformin (Xigduo ABA)

• Type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors: Indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with: 1) heart failure, or 2) type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors.

Coverage Criteria:

For requests of Brenzavvy, Qtern, Segluromet, Steglatro, Steglujan, Invokamet, Invokamet XR, Invokana, brand dapaglifloxin, brand dapagliflozin-metformin:

• Requested drug is being used for a Food and Drug Administration (FDA)-approved indication (see above); AND
• ONE of the following:
  • Trial and failure of a minimum 30-day supply, contraindication, or intolerance to one of the following generics:
    • metformin
    • metformin ER
    • glipizide-metformin
    • glyburide-metformin
    • pioglitazone-metformin
  • Applies to Invokana, Invokamet, and Invokamet XR, only: Patient has one of the following:
    • History of atherosclerotic cardiovascular disease (ASCVD)
    • High risk for ASCVD with multiple risk factors (e.g., obesity, hypertension, smoking, dyslipidemia, albuminuria)
    • Established chronic kidney disease (CKD)
    • Heart failure; AND
• Trial and failure of a minimum 90-day supply, or intolerance to ONE of the following preferred brands:
  • Farxiga
  • Xigduo XR; AND
• Trial and failure of a minimum 90-day supply, or intolerance to ONE of the following:
  • Glyxambi
  • Jardiance
  • Synjardy
  • Synjardy XR
  • Trijardy XR
• Request for nonpreferred brand dapagliflozin (Farxiga ABA) and brand dapagliflozin/metformin (Xigduo XR ABA): Please indicate medical reason why the following agents cannot be used: Farxiga (dapagliflozin) and Xigduo XR (dapagliflozin/metformin) 

For requests of Inpefa:

• Requested drug is being used for a Food and Drug Administration (FDA)-approved indication (see above); AND
• Trial and failure of a minimum 90-day supply, or intolerance to BOTH of the following preferred brands:
  • Farxiga
  • Jardiance

Reauthorization Criteria:

• Documentation of a positive clinical response to therapy.

Coverage Duration:

• Initial: 1 year

• Reauthorization: 1 year

Dosing:

• Dapagliflozin Agents:Farxiga (dapagliflozin)*; Xigduo XR (dapagliflozin/metformin ER)*; Qtern (dapagliflozin/saxagliptin); brand dapagliflozin, brand dapagliflozin-metformin;
  • 5 mg to 10 mg once daily for glycemic control, 10 mg for once daily for all other indications.
• Empagliflozin Agents: Jardiance (empagliflozin)*; Glyxambi (empagliflozin/linagliptin)*; Synjardy (empagliflozin/metformin)*; Synjardy XR (empagliflozin/metformin ER)*; Trijardy XR (empagliflozin/ linagliptin/metformin ER)*
  • 10 mg once daily. May increase to 25 mg once daily for additional glycemic control in adults and pediatric patients 10 years and older.
• Bexagliflozin Agents: Brenzavvy (bexagliflozin)
  • 20mg once daily
• Ertugliflozin Agents: Steglatro (ertugliflozin); Steglujan (ertugliflozin/sitagliptin); Segluromet (ertugliflozin/metformin) 
  • 5 mg once daily. May increase to 15 mg once daily for additional glycemic control.
• Sotagliflozin Agents: Inpefa (sotagliflozin)
  • 200 mg once daily. Up titrate after 2 weeks to 400 mg once daily as tolerated.
• Canagliflozin Agents: Invokana (canagliflozin); Invokamet (canagliflozin/metformin); Invokamet XR (canagliflozin/metformin ER) 
  • 100 mg once daily. May increase to 300 mg once daily for additional glycemic control.

* Preferred SGLT2-I Agents with no step therapy requirements  

Authorization is not covered for the following:

• The use of this drug for indications not listed in this policy does not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.

Additional Information:

• WHA preferred step therapy agents include Farxiga (dapagliflozin), Xigduo XR (dapagliflozin/metformin ER), Jardiance (empagliflozin), Glyxambi (empagliflozin/linagliptin), Synjardy (empagliflozin/metformin), Synjardy XR (empagliflozin/metformin ER), and Trijardy XR (empagliflozin/linagliptin/metformin ER).
• All SGLT2-Is, with the exception of Inpefa (sotagliflozin), are approved to improve glycemic control in T2DM.
• SGLT2-Is are not recommended in patients with type 1 diabetes mellitus (T1DM).
• Dapagliflozin, canagliflozin, empagliflozin, and sotagliflozin have additional indications related to CVD outcomes, CKD, and/or HF.

Policy Updates:

• 05/13/2019 – Steglatro annual review
• 06/11/2019 – Segluromet and Xigduo XR annual reviews
• 02/16/2021 – SGLT2 class review. For SGLT2s, criteria updated, format updated, preferred agents updated, and added heart failure criteria for Farxiga
• 02/15/2022 – New policies for Trijardy XR, Steglujan and Qtern approved by P&T. Farxiga criteria update for new indication to reduce the risk of sustained eGFR decline, end stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression. Added step edit for Farxiga heart failure indication
• 11/15/2022 – Add Glyxambi and Trijardy XR as step agents, require 90-day trial of step agents.
• 12/01/2023 – Place step therapy on Invokana, Invokamet, Invokamet XR. Remove ST on Farxiga and Xigduo XR. Change PA to ST for Brenzavvy, Inpefa and add these newly released agents to criteria. Update ST agents for Steglatro, Segluromet, Steglujan, and Qtern.
• 03/01/2024 – Feb 2024 P&T updated to include ABA products 
• 07/12/2024 – Add reauthorization criteria and update ST on Inpefa

References:

1. Amanda S, Butcher R. Sodium-glucose co-transporter 2 inhibitors for the treatment of type 2 diabetes: a review of clinical effectiveness, cost-effectiveness, and guidelines. CADTH Rapid Response Reports. https://www.ncbi.nlm.nih.gov/books/NBK545104/. Published June 14, 2019. Accessed October 21, 2019.
2. American Diabetes Association. Standards of Medical Care in Diabetes−2020. Diabetes Care. January 2020; 43 (Supplement1). Annotated Jan 1, 2020. https://care.diabetesjournals.org/content/43/Supplement_1.
3. Cosentino F, Cannon CP, Cherney DZI, Masiukiewicz U, Pratley R, Dagogo Jack S, Frederich R, Charbonnel B, Mancuso J, Shih WJ, Terra SG, Cater NB, Gantz I, McGuire DK; VERTIS CV Investigators. Efficacy of Ertugliflozin on Heart Failure-Related Events in Patients with Type 2 Diabetes Mellitus and Established Atherosclerotic Cardiovascular Disease: Results of the VERTIS CV Trial. Circulation. 2020 Oct 7. doi: 10.1161/CIRCULATIONAHA.120.050255.
4. Cannon CP, Pratley R, Dagogo-Jack S, Mancuso J, Huyck S, Masiukiewicz U, Charbonnel B, Frederich R, Gallo S, Cosentino F, Shih WJ, Gantz I, Terra SG, Cherney DZI, McGuire DK; VERTIS CV Investigators. Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes. N Engl J Med. 2020 Oct 8;383(15):1425-1435. doi: 10.1056/NEJMoa2004967
5. Johnston R, Uthman O, Cummins E, et al. Canagliflozin, dapagliflozin and empagliflozin monotherapy for treating type 2 diabetes: systematic review and economic evaluation. Health Technol Assess. 2017;21(2):1-218. doi: 10.3310/hta21020.
6. McMurray JJV, Solomon SD, Inzucchi SE, et al; DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019 Sep 19. doi: 10.1056/NEJMoa1911303.
7. Qtern Prescribing Information. AstraZeneca Pharmaceuticals LP. Wilmington, DE. January 2020.
8. Steglatro Package Insert. Merck & Co. Inc. Whitehouse Station, NJ. January 2020.
9. Steglujan Prescribing Information. Merck & Co., Inc. Whitehouse Station, NJ. November 2021.
10. Segluromet Package Insert. Merck & Co. Inc. Whitehouse Station, NJ. January 2020
11. Trijardy XR Prescribing Information. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT. June 2021.
12. Tehrani D, Brownell NK, Fonarow GC. Vertis CV Trial: Heterogeneity in Clinical benefits of Sodium-glucose Cotransporter-2 inhibitors for Patients with Type II Diabetes. American College of Cardiology. 2020 Sep 1.
13. Zaccardi F, Webb DR, Htike ZZ, Youssef D, Khunti K, Davies MJ. Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis. Diabetes Obes Metab. 2016 Aug;18(8):783-94.
14. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.
15. Wiviott SD, Raz I, Bonaca MP, et al; DECLARE–TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019 Jan 24;380(4):347-357. doi: 10.1056/NEJMoa1812389.
16. Xigduo XR Package Insert. AstraZeneca Pharmaceuticals LP. Wilmington, DE. January 2020.
17. Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019 Jan 5;393(10166):31-39. doi: 10.1016/S0140-6736(18)32590-X.