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Prior Authorization Protocol
BYDUREONTM (exenatide extended-release for injectable suspension), BYETTATM (exenatide), VICTOZAR (liraglutide), SYMLINR, SYMLIN PENR (pramlintide acetate), TANZEUMTM (albiglutide), TRULICITYTM (dulaglutide)




HNMC
Coverage of drugs is first determined by the member’s pharmacy or medical benefit. Please consult with or refer to the Evidence of Coverage document.
  1. FDA Approved Indications:
    • Bydureon, Byetta, Tanzeum, Trulicity, Victoza: An adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
    • Symlin: Adjunctive treatment in patients with type 1 or type 2 diabetes who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy
  2. Health Net Approved Indications and Usage Guidelines:
    Bydureon/ Byetta/Tanzeum/Trulicity/Victoza:
    • Diagnosis of type 2 diabetes
    AND
    • Failure or clinically significant adverse effects to metformin (unless contraindicated)
    Symlin:
    • Diagnosis of Diabetes Mellitus Type 1 or 2

    AND

    • Failure to achieve desired blood glucose level despite 3 months of three or more daily mealtime insulin (e.g. HumalogR, HumulinR R) injections or use of an insulin pump
  3. Coverage is Not Authorized For:
    • Bydureon, Victoza, Tanzeum, Trulicity: Patients with a personal or family history of medullary thyroid carcinoma (MTC) and Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
    • Symlin: Patients with confirmed diagnosis of gastroparesis or taking concomitant drugs altering gastrointestinal motility and agents that alter intestinal absorption of nutrients
    • 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:
    • 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.
    • The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) 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 A1c level 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 ACCORD study with the primary objective of decreasing CVD risk with interventions aimed at achieving an A1c 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 ADVANCE and VADT studies did not demonstrate any excess total or CVD mortality with intensive regimens that achieved A1c 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 A1c 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
    • Bydureon, Tanzeum, Trulicity and Victoza are contraindicated in patients with with a personal or family history of medullary thyroid carcinoma (MTC) and Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
    • Not approvable for appetite suppression or treatment of obesity since currently there are no studies to support the use of Byetta, Tanzuem, Trulicity or Victoza for these conditions. There are no clinical data on the use of Symlin for treatment of weight loss or appetite suppression.
    • 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.
    • 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 Januvia. (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.
    • 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.
    • Symlin has not been evaluated in the pediatric population.
    • Most studies with Symlin have shown reduction in HbA1c of -0.1 to -0.43% in type 1 diabetes from baseline compared to a reduction of -0.3 to -0.62% in type 2 diabetes. Patients with HbA1c >9% should not be considered for Symlin as insulin therapy should first be optimized.
    • The American Association of Clinical Endocrinologists (AACE) considers intensive insulin therapy as three or more insulin injections daily or use of an insulin pump as optimal management for type 1 diabetics as well as for type 2 diabetics who may have insulin deficiency.
    • When initiating Symlin, reduce mealtime insulin doses, including premixed insulins, by 50% to reduce the risk of hypoglycemia. At least 3 days should have elapsed before titrating Symlin to the next dose increment in order to reduce the risk of nausea. Insulin dosage adjustments and close monitoring of blood glucose are required when Symlin is added to one or more antihyperglycemic agent(s).
    • Symlin is used with mealtime insulin therapy and has been associated with an increased risk of insulin-induced severe hypoglycemia, particularly in patients with type 1 diabetes and should not be used in patients with a history of recurrent severe hypoglycemia requiring assistance of another individual or administration of glucagon or IV glucose during the past 6 months. When severe hypoglycemia associated with Symlin use occurs, it is usually seen within the first 2 to 3 hours following a Symlin injection. If severe hypoglycemia occurs while operating a motor vehicle, heavy machinery, or while engaging in other high-risk activities, serious injuries or death may occur. Appropriate patient selection, careful patient instruction, and insulin dose adjustments are critical elements for reducing this risk.
    • Due to its effects on gastric emptying, Symlin should not be considered for patients taking drugs that alter gastrointestinal motility (e.g., anticholinergic agents such as atropine) or medications that slow intestinal absorption of nutrients (e.g., alpha-glucosidase inhibitors). Examples of drugs altering gastrointestinal motility or intestinal absorption of nutrients include: erythromycin, metoclopramide, cholestyramine, WelcholR, ColestidR, LomotilR, LibraxR, DonnatalR, PrecoseR, GlysetR, etc. Symlin slows gastric emptying, which may delay the absorption of concomitantly administered oral medications. The concomitant oral medication should be administered at least 1 hour prior or 2 hours after Symlin injection if rapid onset or threshold concentration of the concomitant medication is a critical determinant of its effectiveness (such as with analgesics, antibiotics, and oral contraceptives).
  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 PO per 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
    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 PO QD

    40 mg/day

    glipizide ER (Glucotrol XLR)

    5-20 mg PO QD

    20 mg/day

    pioglitazone (ActosR)

    15-45 mg PO QD

    45 mg/day

    pioglitazone/ metformin (ACTOplus MetTM)

    15 mg/500 mg PO QD, up to 45 mg/2,550 mg/day

    45 mg/2,550 mg/day

    pioglitazone/glimepiride (DuetactR)

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

    45 mg/8 mg

    JanuviaR (sitagliptin)

    25 mg to 100 mg PO QD

    100 mg day

    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 day

    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 day

    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

    2 mg SC once weekly

    Length of Benefit

    Byetta

    Initiate at 5 mcg SC BID at any time within the 60 minute period before morning and evening meals (or before the 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.

    Length of Benefit

    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.

    Length of Benefit

    Symlin

    Diabetes Mellitus Type II:
    Initiate at 60 mcg SC immediately prior to each major meal (≥250 kcal containing ≥30 gm of carbohydrate)
    and increase to 120 mcg when no clinically significant nausea has occurred for at least 7 days.
    If significant nausea persists at 120 mcg then decrease to 60 mcg
    Diabetes Mellitus Type I:
    Initiate at 15 mcg SC immediately prior to major meal and titrate at 15 mcg increments to maintenance of 30 mcg,
    45 mcg or 60 mcg when no clinically significant nausea has occurred for at least 3 days.
    If significant nausea persists at 45 or 60 mcg, decrease to 30 mcg. If 30 mcg is not tolerated, discontinue Symlin.

    Length of Benefit

    Trulicity

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

    Length of Benefit

    Tanzeum

    30 to 50 mg SC once weekly

    Length of Benefit
  7. Product Availability:
    Bydureon: Single-dose tray: 2 mg vial; Single-dose Pre-filled Pen: 2 mg pen
    Byetta: Pre-filled Pen: 5 mcg/dose (0.02 ml), 60 doses, 1.2 ml pre-filled pen; 10 mcg/dose (0.04 ml), 60 doses, 2.4 ml pre-filled pen
    Tanzeum single dose Pen: 30 mg and 50 mg
    SymlinPen 60 (1000 mcg/ml, two 1.5 ml disposable multidose pen-injector)
    SymlinPen 120 (1000 mcg/ml, two 2.7 ml disposable multidose pen-injector)
    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
    Victoza: Multi-Dose Pre-filled Pen: 6 mg/ml, 3 ml pre-filled pen with 2 pens; 6 mg/ml, 3 ml pre-filled pen with 3 pens
  8. References:
    1. Bydureon [Prescribing information] San Diego, CA: Amylin Pharmaceuticals, Inc; March 2015.
    2. Byetta [Prescribing information] San Diego, CA: Amylin Pharmaceuticals, Inc; February 2015.
    3. Symlin. [Prescribing information] Wilmington, DE:, AstraZeneca Pharmaceuticals, LP; June 2014.
    4. Tanzeum [Prescribing information] Wilmington, DE: GlaxoSmithKline; May 2015.
    5. Trulicity [Prescribing information] Indianapolis, IN: Eli Lilly and Company, Inc; March 2015.
    6. Victoza [Prescribing information] Princeton, NJ: Novo Nordisk Inc March 2015.
    7. Inzucchi, SE, Bergenstal, RM, Buse, JB, et al. Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-Centered Approach Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015;38:140149 | DOI: 10.2337/dc14-2441 Available at: http://care.diabetesjournals.org/content/38/1/140.full.pdf+html. Accessed July 1, 2015.
    8. American Diabetes Association (ADA) Position Statement. Standards of Medical Care in Diabetes2011. Available at: http://care.diabetesjournals.org/content/37/Supplement_1/S14.full.pdf Accessed July 1, 2015.
    9. 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.
    10. 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. Daibetes Care. 2003;26(8):2238-43.
    11. 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):3080-6.
    12. 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):230-5.
    13. 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):187-95.
    14. Chow CC, Tsang LW, Soresen JP, et al. Comparison of insulin with or swithout continuation of oral hypoglycemic agents in the treatment of secondary failure in NIDDM patients. Diabetes Care. 1995;18(3) 307-14.
    15. 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):539-42.
    16. 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.
    17. The ADVANCE Collaborative Group: Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.N Engl J Med. 358:25602572, 2008.
    18. 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].
    19. 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.
    20. 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.
    21. MicromedexR Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. July 1, 2015.
    22. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2008 ; 31(Suppl 1:S12-S54.
    23. The American Association of Clinical Endocrinologists (AACE) medical guidelines for clinical practice for developing a diabetes mellitus comprehensive care plan. Endocrine Practice. 2011;17 (suppl 2).
    24. Buse J, Weyer C, Maggs D, et al. Amylin Replacement with Pramlintide in Type 1 and Type 2 Diabetes: A Physiological Approach to Overcome Barriers With Insulin Therapy. Clinical Diabetes. 20(3):137-144.
    25. Hollander PA, Levy P, Fineman MS, et al. Pramlintide as an adjunct to insulin therapy Improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial. Diabetes Care. 2003 Mar;26(3):784-790.
    26. Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c). Diabetes Care. 2003 Mar;26(3):881-885.
    27. Ratner RE, Dickey R, Fineman M, et al. Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in Type 1 diabetes mellitus: a 1-year, randomized controlled trial. Diabet Med. 2004 Nov;21(11):1204-1212.
    28. Ratner RE, Want LL, Fineman MS et al. Adjunctive therapy with the amylin analogue pramlintide leads to a combined improvement in glycemic and weight control in insulin-treated subjects with type 2 diabetes. Diabetes Technol Ther. 2002;4:51-61.
    29. Whitehouse F, Kruger DF, Fineman M, et al. A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes. Diabetes Care. 2002;25:724-730.
    30. Institute of Safe Medication Practices June 16, 2005. Available at: http://www.ismp.org/newsletters/acutecare/articles/20050616.asp. July 1, 2015..
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.