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DESCRIPTIONByetta (exenatide) and Victoza (liraglutide), anti-hyperglycemic medications for subcutaneous (SC) injection, are incretin mimetic medications that bind and activate the human glucagon-like peptide01 (GLP-1) receptor. Activation of this receptor increases glucose-dependent insulin secretion by pancreatic beta-cells, suppresses glucagon secretion, and slows gastric emptying.
Byetta and Victoza are approved by the Food and Drug Administration (FDA) as an adjunct to diet and exercise to improve glycemic control in patients with Type 2 diabetes. Byetta is administered SC twice daily, while Victoza is a once daily SC injection.
Another medication in this drug class, Bydureon, is not currently covered on the BCBSMS formulary.
To achieve and maintain this goal, the algorithm provides a set of tier 1 well-validated therapies that includes 3 steps. The first step in the algorithm is to make lifestyle changes and start metformin. If lifestyle intervention and the maximal tolerated dose of metformin fail to achieve or sustain the glycemic goals another medication needs to be added. This second step includes the addition of either insulin or a second-generation sulfonylurea (glimepiride, glipizide, and their extended formulations are preferred). If lifestyle, metformin, and sulfonylurea or basal insulin do not result in target glycemia levels, Step 3 should be to start or intensify insulin therapy. When insulin injections are started, insulin secretagogues (sulfonylurea or glinides) should be discontinued, or tapered and then discontinued, since they are not considered to be synergistic. Although addition of a third oral agent can be considered, this approach is usually not preferred as it is no more effective in lowering glycemia and is more costly than initiating or intensifying insulin.3
The algorithm also includes a second tier of less well-validated therapies. In selected clinical settings, this algorithm may be considered. When hypoglycemia is particularly undesirable, the addition of exenatide or pioglitazone may be considered. If promotion of weight loss is a major consideration and the A1C is close to target, exenatide is an option. The algorithm does not recommend the use of rosiglitazone.3
Medications not included or excluded in tier 1 and 2 are considered ‘other therapies’ in the algorithm. Although these medications may have a place in certain T2DM patients, they are not the preferred medications due to a variety of clinical reasons (i.e., µ-glucosidase inhibitors have frequent gastrointestinal side effects and need to be taken 3 times daily; glinides are associated with weight gain, hypoglycemia and have to be taken 3 times daily; and DDP-4 inhibitors have not established their long-term safety).3
The algorithm notes that the expected decrease in A1C with monotherapy is 0.5-1.0 with exenatide. Advantages of exenatide are the weight loss associated with use (2-3 kg over 6 months) and the lack of hypoglycemia. Disadvantages include two injections daily, frequent GI side effects (30-45% of treated patients experience one or more episodes of nausea, vomiting, or diarrhea), and the long-term safety has not been established. GI side effects tend to abate over time.3
The American Association of Clinical Endocrinologist/American College of Endocrinology (AACE/ACE) consensus panel on type 2 diabetes mellitus wrote an algorithm for glycemic control.4 Metformin is considered the cornerstone of medication therapy for most patients as in the ADA algorithm. However, exenatide is considered a second line preferred component because of its safety, with nearly complete absence of hypoglycemia and because of its potential for inducing weight loss. Also, the algorithm notes that it has the ability to inhibit glucagon secretion in a glucose-dependent manner after consumption of meals, to increase satiety, and to delay gastric emptying.4
There is one head-to-head trial published that compared liraglutide to exenatide.5 It was a 26 week open label, parallel group study of 464 T2DM patients inadequately controlled on maximally tolerated doses of metformin, sulfonylurea, or both who were randomized to additional liraglutide 1.8 mg SC once daily (n=233) or exenatide 10 mcg SC twice daily (n=231). The primary outcome was change in A1C. Liraglutide reduced mean A1C significantly more than exenatide (-1.12% [SE 0.08] vs -0.79% [0.08]; estimated treatment difference -0.33; 95% CI -0.47 to -0.18; p<0.0001). Weight loss was similar between groups with patients losing 3.24 kg with liraglutide versus 2.87 kg exenatide, p>0.05. Nausea was significantly less persistent with liraglutide than with exenatide (estimated treatment rate ratio 0.448, p<0.0001). Minor hypoglycemia was significantly less frequent with liraglutide than with exenatide (1.93 vs 2.60 events per patients per year; rate ratio 0.55; 95% CI 0.34 to 0.88; p=0.0131; 25.5% vs 33.6% had minor hypoglycemia). A 14-week extension study found switching from exenatide to liraglutide significantly reduced mean A1C from 7.2% at week 26 to 6.9% at week 40 (-0.32 ± 0.043%; p<0.0001), but remained similar with continued liraglutide (7.0% to 6.9%; -0.06 ± 0.041%, p=0.1222).6 The group that switched from exenatide to liraglutide and the group that continued liraglutide tolerated liraglutide well. Calcitonin levels remained at the lower level of the normal range (<1 pg/mL) and did not differ between groups. No medullary thyroid carcinoma or pancreatitis cases were reported during the extension.
A review was conducted to evaluate the possible association between GLP-1 agonist use and pancreatitis in patients with T2DM.7 Clinical trials for exenatide and liraglutide and postmarketing reports for exenatide have demonstrated that patients with T2DM have developed acute pancreatitis while taking these medications.7 Several retrospective cohort studies have not shown an increased risk of pancreatitis in patients taking exenatide.7 Based on recommendations from the FDA, the current prescribing information for exenatide includes a warning about the risk of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis.1 Prescribing information for exenatide and liraglutide includes a warning about the risk of pancreatitis, without specific mention of type or severity.2,8
POLICYEffective 01/01/2013, step therapy is required for new start prescriptions for Byetta and Victoza when purchased at a pharmacy. Sampling will not be acceptable for patient being on stable therapy.
BCBSMS covers Byetta and Victoza with prior authorization when the member meets all of the criteria for one of the following conditions:
POLICY EXCEPTIONSStep therapy for Byetta/Victoza is not required for Federal Employee Program (FEP) and State Health Plan members.
POLICY GUIDELINESInvestigative service is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized by certifying boards and/or approving or licensing agencies or published peer review criteria as standard, effective medical practice for the treatment of the condition being treated and as such therefore is not considered medically necessary.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
POLICY HISTORY11/30/2012: New policy added. Effective 01/01/2013.
This may not be a comprehensive list of procedure codes applicable to this policy.
The code(s) listed below are ONLY medically necessary is the procedure is performed according to the "Policy" section of this document.