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Prior Authorization Protocol
BYDUREONTM (exenatide extended-release for injectable suspension),
BYETTATM (exenatide), TRULICITYTM (dulaglutide), VICTOZAR (liraglutide)


NATL
Coverage of drugs is first determined by the memberís pharmacy or medical benefit. Please consult with or refer to the Evidence of Coverage document.
  1. FDA Approved Indications:
    • An adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
  2. Health Net Approved Indications and Usage Guidelines:
    • Diagnosis of type 2 diabetes with HbA1c greater than 6.5% (within the last 6 months for new starts on Byetta/Bydureon/Trulicity/Victoza therapy)

    AND

      • Clinically significant adverse effects to metformin (unless contraindicated)

    OR

      • Failure to achieve HbA1c less than or equal to 6.5% while on metformin at a dose of at least 1500 mg per day
  3. Coverage is Not Authorized For:
    • Bydureon, Victoza, Trulicity: Patients with a personal or family history of medullary thyroid carcinoma (MTC)
    • Bydureon, Victoza, Trulicity: Patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
    • Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section unless there is sufficient documentation of efficacy and safety in the published literature.
  4. General Information:
    • Byetta and Victoza have not been studied sufficiently in patients with a history of pancreatitis. In clinical trials, there were 7 cases of pancreatitis among Victoza-treated patients and 1 case among comparator-treated patients. Byetta has been associated with acute pancreatitis in postmarketing data.
    • The American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) and American Diabetes Association (ADA) state that because of its safety and efficacy, metformin is the cornerstone of monotherapy and is usually the most appropriate initial choice for monotherapy unless there is a contraindication, such as renal disease, hepatic disease, gastrointestinal intolerance, or risk of lactic acidosis.
    • Not approvable for appetite suppression or treatment of obesity since currently there are no studies to support the use of Byetta or Victoza for these conditions.
    • Byetta has shown HbA1c reductions of 0.4 to 0.9% in clinical studies conducted in patients who have not achieved adequate glycemic control with sulfonylureas, metformin or combination of both. The mean baseline HbA1c levels ranged from 8.2 to 8.6%. Byetta added to a thiazolidinedione, with or without metformin, has shown 0.8% reduction in HbA1c. The mean baseline HbA1c was 7.9% for both groups. For patients with poorly controlled diabetes (e.g., HbA1c > 9%), insulin therapy may be a more appropriate therapeutic alternative.
    • Victoza has shown a mean HbA1c reduction of 1% to 1.5% for the total populations in the trials in combination with metformin, sulfonylureas, combinations of both and with thiazolidinedione (LEAD-1 through LEAD-6). The mean baseline HbA1c for all LEAD studies was in a range from 8.2 to 8.5%. Victoza showed up to a 2.7% reduction in patients with inadequate glycemic control (mean baseline of 9.5% while failing metformin). Victoza's product labeling includes data showing superior blood glucose control and weight reduction when compared to JanuviaR (sitagliptin). The label also includes approval to add basal insulin to Victoza in combination with metformin for adults with type 2 diabetes. Victoza's product labeling includes data showing superior blood glucose control and weight reduction when compared to Januvia (sitagliptin). The label also includes data to support the addition of Levemir (insulin detemir) to Victoza in combination with metformin for adults with type 2 diabetes. Victoza has not been studied in combination with prandial (mealtime) insulin.
    • The ADA and the European Association for the Study of Diabetes (EASD) 2009 treatment algorithm on the approach to management of hyperglycemia in individuals with type 2 diabetes recommends lifestyle interventions (diet and exercise) plus metformin as the initial therapy. Patients not achieving goal are then recommended to receive other well-validated therapies such as basal insulin (considered rapidly effective) or a sulfonylurea (considered the least expensive) in combination with lifestyle interventions and metformin. When hypoglycemia is particularly undesirable, addition of less well-validated therapies, pioglitazone (a thiazolidinedione considered to have a low incidence of hypoglycemia) in addition to metform or a GLP-1 agonist (if weight loss is a major consideration and the A1clevel is close to target) in addition to metformin may be considered.
    • The most recent glycemic goal recommended by ADA is an A1c level <7% and the goal set by AACE is <6.5%, which is considered closer to normal
    • The recent clinical trials have aimed to reach A1c levels less than or equal to 6.5% with a variety of interventions. The results of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with the primary objective of decreasing cardiovascular disease (CVD) risk with interventions aimed at achieving an HbA1c level of <6% vs. <7.9%, showed excess CVD mortality in the intensive treatment group (2.6% vs. 1.8%, p=0.02) and more deaths from any cause than the standard-treatment group (5% vs. 4%, p=0.04). Results from Action in Diabetes and Vascular Disease: Perterax and Diamicron MR Controlled Evaluation (ADVANCE) and Veterans Affairs Diabetes Trial (VADT) studies did not demonstrate any excess total or CVD mortality with intensive regimens that achieved HbA1c levels comparable with the 6.5 % in ACCORD. None of the studies demonstrated a benefit of intensive glycemic control on the primary CVD outcomes. Clinical judgment based on the potential benefits and risk of reaching more stringent HbA1c goals should be applied for every patient. Factors such as life expectancy, risk of hypoglycemia, and the presence of CVD should be considered before intensifying the therapeutic regimen.
    • Trulicity has not been studied sufficiently in patients with a history of pancreatitis. In clinical trials, there was 1 reported case of chronic pancreatitis and 1 case of pancreatic cancer for Trulicity treated patients. Additionally, there were 3 reported cases of acute pancreatitis in the comparator-treated patients.
    • Trulicity has shown a mean HbA1C reduction of 0.7% as monotherapy. The mean HbA1c reduction for total populations in the trials was 0.7 to 1.64% in combination with metformin, pioglitazone, combinations of both, or prandial insulin therapy (AWARD-1 through AWARD-6). The mean baseline for HbA1c for all AWARD studies was 7.6 to 8.1%. Trulicity showed up to a 1.6% reduction in HbA1c in combination with insulin lispro. Trulicity is the only GLP-1 receptor agonist studied in combination with prandial insulin therapy. The results of the trials showed superiority of Trulicity to reduce HbA1c from baseline when compared to Byetta (exenatide), Lantus (Insulin Glargine), and Januvia (sitagliptin). Trulicity 1.5 mg once weekly was non-inferior to Victoza (liraglutide) titrated to 1.8 mg once daily.
    • There is a black box warning for Trulicity. Trulicity is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Due to serious risks associated with Trulicity, the FDA approved the drug with a Risk Evaluation and Mitigation Strategy (REMS).
  5. Therapeutic Alternatives:
    Drug Dosing Regimen Dose Limit/ Maximum Dose

    metformin (GlucophageR)

    500 mg BID or 850 mg PO QD, titrate up to 2,550 mg/day

    2,550 mg/day

    metformin ER (GlucophageR XR)

    500 mg PO QD, increase up to 2,000 mg/day

    2,000 mg/day

    GlumetzaR (metformin ER)

    1000 mg PO QD, increase up to 2,000 mg/day

    2,000 mg/day

    glyburide/metformin (GlucovanceR)

    1.25/250 mg PO QD, up to 20/2,000 mg/day

    20/2,000 mg/day

    glipizide/metformin (MetaglipTM)

    Initial therapy:
    2.5/250 mg PO QD to 10/1,000 mg or 10/2,000 mg in divided doses
    Second-line therapy (patients not adequately controlled on glipizide or metformin):
    2.5/500 mg or 5/500 PO BID to 20/2,000 mg/day
    Initial therapy:
    10/1,000 mg/day or 10/2,000 mg/day
    Second-line therapy:
    20/2,000 mg/day

    glyburide (MicronaseR, DiabetaR)

    2.5-5 mg PO QD, up to 20 mg/day

    20 mg/day

    glyburide, micronized (GlynaseR Pres Tab)

    1.5 to 3 mg/ PO QD up to 12 mg/day

    12 mg/day

    glimepiride (AmarylR)

    1-2 mg PO QD, up to 8 mg/day

    8 mg/day

    glipizide (GlucotrolR)

    5-40 mg/day PO QD

    40 mg/day

    glipizide ER (Glucotrol XLR)

    5-20 mg/day PO QD

    20 mg/day

    pioglitazone (ActosR)

    15-45 mg/day PO QD

    45 mg/day

    ACTOplus MetTM (pioglitazone/ metformin)

    15 mg/500 mg PO QD, up to 45 mg/2,250 mg/day

    45 mg/2,550 mg/day

    pioglitazone/glimepiride (DuetactR)

    30 mg/2 mg PO QD, up to 45 mg/8 mg/day

    45 mg/8 mg

    JanuviaR (sitagliptin)

    25 mg to 100 mg PO QD

    100 mg QD

    JanumetR (sitagliptin/metformin)

    50 mg/500 mg, 50 mg/1,000 mg PO BID

    100 mg sitagliptin and 2,000 mg metformin

    Janumet-XRR (sitagliptin/metformin extended release)

    50 mg/500 mg, 50 mg/1,000 mg, 100 mg/1,000 mg PO QD

    100 mg sitagliptin and 2,000 mg metformin

    OnglyzaR (saxagliptin)

    2.5 mg to 5 mg PO QD

    5 mg QD

    Kombiglyze-XRR (saxagliptin/metformin extended release)

    5 mg/500 mg, 2.5 mg/1,000 mg, 5 mg/1,000 mg PO QD

    5 mg saxagliptin and 2,000 mg metformin

    TradjentaR (linagliptin)

    5 mg PO QD

    5 mg QD

    JentaduetoR (linagliptin/metformin)

    2.5 mg/500 mg, 2.5 mg/850 mg, 2.5 mg/1,000 mg PO BID

    5 mg linagliptin and 2,000 mg metformin

    HumalogR (insulin lispro)

    0.5 to 1 U/kg SC QD

    Individualize dosage

    HumulinR R (regular insulin human)

    0.5 to 1 U/kg SC QD

    Individualize dosage

    HumulinR N (NPH human isophane)

    0.5 to 1 U/kg SC QD

    Individualize dosage

    LantusR (insulin glargine)

    DM Type 2 (Insulin naive):
    Start at 10U SC QD, maintenance dose ranges from 2-100 U/day.
    Switching from once-daily NPH:
    Same total daily dosing
    Switching from twice-daily NPH:
    Reduce Lantus dose by 20% at initiation

    Individualize dosage

    LevemirR (insulin detemir)

    Insulin-naive patients with Type 2 diabetes:
    Start at 0.1 to 0.2 U/ kg SC QD in the evening or 10 units QD or BID,
    and adjust the dose to achieve glycemic targets.
    Patients with type 1 or 2 currently receiving only basal insulin or basal-bolus:
    Switch can be done on a unit-to-unit basis for changing the basal insulin to Levemir.

    Individualize dosage

    * Requires Prior Authorization
  6. Recommended Dosing Regimen and Authorization Limit:
    Drug Dosing Regimen Authorization Limit

    Bydureon

    Administer 2 mg SC once every seven days

    Initial authorization for 6 months (4 vials or pens/month).
    If inadequate response to Bydureon (e.g., HbA1c > 7%) at the end of initial authorization period,
    either a switch to insulin therapy, addition of insulin(s) to Bydureon or a referral to an endocrinologist will be required.

    Re-authorization
    Length of Benefit
    For AHCS requests: One Year

    Byetta

    Initiate at 5 mcg SC BID at any time within the 60 minute period before morning and evening meals (or before two main meals of the day, approximately 6 hours or more apart).
    Based on clinical response, increase the dose to 10 mcg SC BID after 1 month.
    Initial authorization for 6 months (1 pen/month)
    If inadequate response to Byetta (e.g., HbA1c > 7%) at the end of initial authorization period, either a switch to insulin therapy,
    addition of insulin(s) to Byetta or a referral to an endocrinologist will be required.

    Re-authorization
    Length of Benefit
    For AHCS requests: One Year

    Victoza

    Initiate at 0.6 mg SC QD for 1 week.
    After one week at 0.6 mg QD, increase dose to 1.2 mg SC QD.
    If 1.2 mg QD does not result in acceptable glycemic control, dose may increase to 1.8 mg SC QD.
    Initial authorization for 6 months (up to 3 pens/month based on dose)
    If inadequate response to Victoza (e.g., HbA1c > 7%) at the end of initial authorization period,
    either a switch to insulin therapy, addition of insulin(s) to Victoza or a referral to an endocrinologist will be required.

    Re-authorization
    Length of Benefit
    For AHCS requests: One Year

    Trulicity

    Initial dose of 0.75 mg SC once weekly, up to 1.5 mg SC once weekly for additional glycemic control

    Initial authorization for 6 months

    If inadequate response to Trulicity (e.g., A1c > 7%) at the end of initial authorization period, either a switch to insulin therapy, addition of insulin(s) to Trulicity or a referral to an endocrinologist will be required.
  7. Product Availability:
    Bydureon: Single-dose tray: 2 mg vial; Single-dose Pre-filled Pen: 2 mg pen
    Byetta: Prefilled Pen: 5 mcg/dose (0.02 ml), 60 doses, 1.2 ml prefilled pen; 10 mcg/dose (0.04 ml), 60 doses, 2.4 ml prefilled pen
    Victoza: Multi-Dose Pre-filled Pen: 6 mg/ml, 3 ml prefilled pen with 2 pens; 6 mg/ml, 3 ml prefilled pen with 3 pens
    Trulicity: Prefilled single-dose pen 0.75 mg/0.5ml, 1.5 mg /0.5ml; Prefilled single-dose syringe 0.75 mg/0.5ml, 1.5 mg /0.5ml
  8. References:
    1. Bydureon [Prescribing information] San Diego, CA: Amylin Pharmaceuticals, Inc; May 2014.
    2. Victoza [Prescribing information] Princeton, NJ: Novo Nordisk Inc; April 2013.
    3. Byetta [Prescribing information] San Diego, CA: Amylin Pharmaceuticals, Inc; February 2013.
    4. Trulicity [Prescribing information] Indianapolis, IN: Eli Lilly and Company, Inc; September 2014.
    5. American Diabetes Association (ADA) Position Statement. Standards of Medical Care in Diabetes2011. Available at: http://care.diabetesjournals.org/content/34/Supplement_1/S11.full. Accessed July 15, 2011.
    6. Nathan DM, et al. Medical management of hyperglycemia in type 2 diabetes: A Consensus algorithm for the initiation and adjustment of therapy-A consensus statement from the ADA and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2009 (32): 193-203.
    7. Shwartz S, Sievers R, Strange P, et al. Insulin 70/30 mix plus metformin versus triple oral therapy in the treatment of type 2 diabetes after failure of two oral drugs: efficacy, safety, and cost analysis. Diabetes Care. 2003;26(8):2238-2243.
    8. Riddle MC, Rosenstock J, Gerich J, et al. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003;26(11):3080-3086.
    9. Aljabri K, Kozak SE, Thompson DM. Addition of pioglitazone or bedtime insulin to maximal doses of sulfonylurea and metformin in type 2 diabetes patients with poor glucose control: a prospective, randomized trial. Am J Med. 2004;116(4):230-235.
    10. Malone JK, Beattie SD, Campaigne BN, et al. Therapy after single oral agent failure: adding a second oral agent or an insulin mixture? Diabetes Res Clin Pract. 2003;62(3):187-195.
    11. Chow CC, Tsang LW, Soresen JP, et al. Comparison of insulin with or without continuation of oral hypoglycemic agents in the treatment of secondary failure in NIDDM patients. Diabetes Care. 1995;18(3) 307-314.
    12. Trischitta V, Italia S, Mazzarino S, et al. Comparison of combined therapies in treatment of a secondary failure to glyburide. Diabetes Care. 1992;15(4):539-542.
    13. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study Group: Effects of intensive glucose lowering in type 2 diabetes.N Engl J Med. 358:25452559, 2008.
    14. The ADVANCE Collaborative Group: Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.N Engl J Med. 358:25602572, 2008.
    15. Abraira C, Duckworth WC, Moritz T: Glycaemic separation and risk factor control in the Veterans Affairs Diabetes Trial (VADT): an interim report. Diabetes Obes Metab. 29 July 2008 [Epub ahead of print].
    16. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2008;31:111.
    17. Rodbard, H., Jellinger, P., et al (2009). Consensus Panel on Type 2 Diabetes Mellitus: An Algorithm for Glycemic Control. Endocrine Practice. 15(6), 540-559.
    18. MicromedexR Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed June 2013.
The material provided to you are guidelines used by this plan to authorize, modify or determine coverage for persons with similar illnesses or conditions. Specific care and treatment may vary depending on individual need and the benefits covered under your contract.