Clinical Policy: GLP-1 Receptor Agonists Reference Number: CP.HNMC.16 Effective Date: 11.16.16 Last Review Date: 11.17 Revision Log Line of Business: Medicaid – Medi-Cal See Important Reminder at the end of this policy for important regulatory and legal information. Description The following are GLP-1 Receptor Agonists requiring prior authorization: lixisenatide (Adlyxin™), Exenatide Extended-Release (Bydureon®), Exenatide (Byetta®), Pramlintide Acetate (Symlin®), Albiglutide (Tanzeum®), Dulaglutide (Trulicity®), Liraglutide (Victoza®), Liraglutide and insulin degludec (Xultophy®),Insulin glargine and lixisenatide (Soliqua®). FDA approved indication Adlyxin, Bydureon, Byetta, Tanzeum, Trulicity, Victoza are indicated: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Adlyxin limitation of use: Has not been studied in patients with chronic pancreatitis or a history of unexplained pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis. Not for treatment of type 1 diabetes or diabetic ketoacidosis. Has not been studied in combination with short acting insulin. Has not been studied in patients with gastroparesis and is not recommended in patients with gastroparesis. Bydureon limitation of use: Not recommended as first-line therapy for patients inadequately controlled on diet and exercise. Should not be used to treat type 1 diabetes or diabetic ketoacidosis. Use with insulin has not been studied and is not recommended. Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis. Byetta limitation of use: Not a substitute for insulin. Byetta should not be used for the treatment of type 1 diabetes or diabetic ketoacidosis. Concurrent use with prandial insulin has not been studied and cannot be recommended. Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis. Tanzeum, Trulicity limitation of use: Not recommended as first-line therapy for patients inadequately controlled on diet and exercise. Page 1 of 16 CLINICAL POLICY GLP-1 Receptor Agonists Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis. Not for treatment of type 1 diabetes mellitus or diabetic ketoacidosis. Not for patients with pre-existing severe gastrointestinal disease. Has not been studied in combination with prandial insulin. Victoza limitation of use: Not recommended as first-line therapy for patients inadequately controlled on diet and exercise. Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis. Not for treatment of type 1 diabetes mellitus or diabetic ketoacidosis. Has not been studied in combination with prandial insulin. Symlin is indicated: For patients with type 1 or type 2 diabetes who use mealtime insulin and have failed to achieve desired glycemic control despite optimal insulin therapy. Soliqua is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus inadequately controlled on basal insulin (less than 60 units daily) or lixisenatide Soliqua limitation of use: Has not been studied in patients with a history of unexplained pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis. Not recommended for use in combination with any other product containing lixisenatide or another GLP-1 receptor agonist. Not for treatment of type 1 diabetes mellitus or diabetic ketoacidosis. Not recommended for use in patients with gastroparesis. Has not been studied in combination with prandial insulin. Xultophy is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus inadequately controlled on basal insulin (less than 50 units daily) or liraglutide (less than or equal to 1.8 mg daily Xultophy limitations of use: Not recommended as first-line therapy for patients inadequately controlled on diet and exercise. Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis. Not recommended for use in combination with any other product containing liraglutide or another GLP-1 receptor agonist. Not for treatment of type 1 diabetes mellitus or diabetic ketoacidosis. Has not been studied in combination with prandial insulin Page 2 of 16 CLINICAL POLICY GLP-1 Receptor Agonists Policy/Criteria Provider must submit documentation (which may include office chart notes and lab results) supporting that member has met all approval criteria. It is the policy of health plans affiliated with Centene Corporation® that Adlyxin, Bydureon, Byetta, Soliqua, Symlin, Tanzeum, Trulicity, Victoza, and Xultophy are medically necessary when the following criteria are met: I. Initial Approval Criteria A. Adlyxin, Bydureon, Byetta, Soliqua, Tanzeum*, Trulicity, Victoza, or Xultophy Requests (must meet all): 1. Diagnosis of type 2 diabetes mellitus; 2. Failure of at least a 3 month trial of metformin unless contraindicated or clinically significant adverse effects are experienced; 3. Dose does not exceed: 20 mcg/day for Adlyxin, 2 mg/week for Bydureon, 20 mcg/day for Byetta, 60 units/20 mcg/day for Soliqua, 50 mg/week for Tanzeum*, 1.5 mg/week for Trulicity, 1.8 mg/day for Victoza, and 50 units/1.8 mg/day for Xultophy. Approval duration: Length of Benefit *Tanzeum is being discontinued. Requests should be discussed with the provider to ensure the provider is aware this product will be removed from the market. B. Symlin Requests (must meet all): 1. Diagnosis of type 1 or type 2 diabetes mellitus; 2. Failure to achieve desired blood glucose level despite 3 months of three or more daily mealtime insulin (e.g. Humalog, Humulin R) injections or use of an insulin pump unless contraindicated or clinically significant adverse effects are experienced; 3. Dose does not exceed 60 mcg prior to each major meal for Symlin in patients with type 1 diabetes and 120 mcg prior to each major meal for Symlin in patients with type 2 diabetes. Approval duration: Length of Benefit C. Other diagnoses/indications 1. Refer to CP.CPA.09 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized). II. Continued Therapy A. Adlyxin, Bydureon, Byetta, Soliqua, Tanzeum*, Trulicity, Victoza, or Xultophy Requests (must meet all): 1. Currently receiving medication via health plan benefit or member has previously met initial approval criteria; 2. Dose does not exceed 20 mcg/day for Adlyxin, 2 mg/week for Bydureon, 20 mcg/day for Byetta, 60 units/20 mcg/day for Soliqua, 50 mg/week for Tanzeum*, 1.5 mg/week for Trulicity, 1.8 mg/day for Victoza, and 50 units/1.8 mg/day for Xultophy. Approval duration: Length of Benefit *Tanzeum is being discontinued. Requests should be discussed with the provider to ensure the provider is aware this product will be removed from the market. Page 3 of 16 CLINICAL POLICY GLP-1 Receptor Agonists A. Symlin Requests (must meet all): 1. Currently receiving medication via health plan benefit or member has previously met initial approval criteria; 2. Documentation of positive response to therapy (e.g., A1c < 7%) at end of initial authorization period; 3. Dose does not exceed 60 mcg prior to each major meal for Symlin in patients with type 1 diabetes and 120 mcg prior to each major meal for Symlin in patients with type 2 diabetes. Approval duration: Length of Benefit B. Other diagnoses/indications (must meet 1 or 2): 1. Currently receiving medication via health plan benefit and documentation supports positive response to therapy. Approval duration: Duration of request or 12 months (whichever is less); or 2. Refer to CP.CPA.09 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized). III. Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policy – CP.CPA.09 or evidence of coverage documents B. Bydureon, Tanzeum, Trulicity, Victoza: Patients with a personal or family history of medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia syndrome type 2 (MEN 2). C. Symlin: Patients with confirmed diagnosis of gastroparesis or taking concomitant drugs altering gastrointestinal mobility and agents that alter intestinal absorption of nutrients. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key A1c or HbA1c: glycated hemoglobin test CVD: cardiovascular disease AACE: American Association of Clinical EASD: European Association for the Study Endocrinologists of Diabetes ACE: American College of Endocrinology GLP-1: glucagon-like peptide-1 ACCORD: Action to Control LEAD: Liraglutide Effect and Action in Cardiovascular Risk in Diabetes trial Diabetes trial ADA: American Diabetes Association MEN 2: multiple endocrine neoplasia AWARD: Assessment of Weekly syndrome type 2 Administration of LY2189265 MTC: medullary thyroid carcinoma (Dulaglutide) in Diabetes SC: subcutaneously Appendix B: General Information GlaxoSmithKline (GSK), manufacturer of Tanzeum, is discontinuing the commercial sale of