FDA APPROVED IONDICATIONS AMYLIN ANALOG: SymlinPen SymlinPen is indicated as an 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.
GLP-1 RECEPTOR AGONIST: Adlyxin Adlyxin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use • Adlyxin 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. • Adlyxin should not be used in patients with type 1 diabetes mellitus. • Adlyxin has not been studied in patients with gastroparesis and is not recommended in patients with gastroparesis. Bydureon BCise Bydureon BCise is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus. Limitations of Use • Bydureon BCise is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise because of the uncertain relevance of the rat thyroid C- cell tumor findings to humans. • Bydureon BCise is not indicated for use in patients with type 1 diabetes mellitus. • Bydureon BCise is an extended-release formulations of exenatide and should not be used with other products containing the active ingredient exenatide. • Bydureon BCise has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis. Byetta Byetta is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use • Byetta is not indicated for use in patients with type 1 diabetes. • Byetta contains exenatide and should not be used with other products containing the active ingredient exenatide. Byetta has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis. Ozempic Ozempic is indicated: • as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. • to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non- fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease. Limitations of Use • Ozempic has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis. • Ozempic is not indicated for use in patients with type 1 diabetes mellitus. Rybelsus Rybelsus is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use • Rybelsus has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis. • Rybelsus is not indicated for use in patients with type 1 diabetes mellitus. Trulicity Trulicity is indicated: • As an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes mellitus. • To reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non- fatal stroke) in adults with type 2 diabetes mellitus who have established cardiovascular disease or multiple cardiovascular risk factors. Limitations of Use • Trulicity has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis. • Trulicity should not be used in patients with type 1 diabetes mellitus. • Trulicity has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis and is therefore not recommended in these patients. Victoza Victoza is indicated: • as an adjunct to diet and exercise to improve glycemic control in patients 10 years and older with type 2 diabetes mellitus. • to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non- fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease. Limitations of Use • Victoza should not be used in patients with type 1 diabetes mellitus. • Victoza contains liraglutide and should not be coadministered with other liraglutide-containing products.
GIP/GLP-1 RECEPTOR AGONIST: Mounjaro Mounjaro is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use • Mounjaro has not been studied in patients with a history of pancreatitis. • Mounjaro is not indicated for use in patients with type 1 diabetes mellitus.
SGLT2 INHIBITOR: Brenzavvy Brenzavvy is 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 in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients. Farxiga Farxiga (dapagliflozin) is indicated: • 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. • To reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure. • To reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established cardiovascular disease or multiple cardiovascular risk factors. • As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use • Farxiga is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients • Farxiga is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m2. Farxiga is likely to be ineffective in this setting based upon its mechanism of action. • Farxiga is not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for kidney disease. Farxiga is not expected to be effective in these populations. Invokana Invokana (canagliflozin) is indicated: • as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. • 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). • 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/1.73m2. Invokana is likely to be ineffective in this setting based upon its mechanism of action. Jardiance Jardiance is indicated: • to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure. • to reduce the risk of sustained decline in eGFR, end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease at risk of progression. • to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease. • as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus, Limitation of Use Jardiance is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients. Jardiance is not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 30 mL/min/1.73 m2. Jardiance is likely to be ineffective in this setting based upon its mechanism of action. Jardiance is not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of intravenous immunosuppressive therapy or greater than 45 mg of prednisone or equivalent for kidney disease. Jardiance is not expected to be effective in these populations. Steglatro Steglatro is 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.
SGLT2 INHIBITOR / METFORMIN: Invokamet, Invokamet XR Invokamet and Invokamet XR are a combination of canagliflozin and metformin hydrochloride (HCl) indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. 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). 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 Invokamet/Invokamet XR is not recommended in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients. Segluromet Segluromet is 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. Synjardy, Synjardy XR Synjardy and Synjardy XR are a combination of empagliflozin and metformin hydrochloride (HCl) indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Empagliflozin, when used as a component of Synjardy/Synjardy XR, is indicated in adults with type 2 diabetes mellitus to reduce the risk of: • Cardiovascular death in adults with established cardiovascular disease. • Cardiovascular death and hospitalization for heart failure in adults with heart failure. Limitation of Use • Synjardy/Synjardy XR are not recommended for patients with type 1 diabetes It may increase the risk of diabetic ketoacidosis in these patients. • Because of the metformin component, Synjardy/Synjardy XR is not recommended for use in patients with heart failure without type 2 diabetes mellitus. Xigduo XR Xigduo XR is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Dapagliflozin is indicated to reduce: • the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and established cardiovascular disease (CVD) or multiple cardiovascular (CV) risk factors. • the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure (NYHA class II-IV) with reduced ejection fraction. • the risk of sustained estimated glomerular filtration rate decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression. Limitation of Use • Xigduo XR is not recommended for patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients. • Because of the metformin component, the use of Xigduo XR is limited to adults with type 2 diabetes for all indications. • Xigduo XR is not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for kidney disease. Xigduo XR is not expected to be effective in these populations.
SGLT2 INHIBITOR / DPP-4 INHIBITOR: Glyxambi Glyxambi is a combination of empagliflozin and linagliptin indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Empagliflozin is indicated to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease. Limitations of Use Glyxambi is not recommended for patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients. Glyxambi has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using Glyxambi. Glyxambi is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 30 ml/min/1.73m2. Glyxambi is likely to be ineffective in this setting based upon its mechanism of action. Qtern Qtern is 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. Steglujan Steglujan is 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. • 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.
SGLT2 INHIBITOR / DPP-4 INHIBITOR / METFORMIN: Trijardy XR Trijardy XR is a combination of empagliflozin, linagliptin, and metformin hydrochloride (HCl) indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Empagliflozin is indicated to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease. Limitations of Use Trijardy XR is not recommended for patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients. Trijardy XR has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using Trijardy XR.
Long Acting Insulin / GLP-1 RECEPTOR Agonist: Soliqua Soliqua 100/33 is a combination of insulin glargine and lixisenatide and is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use: • Soliqua 100/33 has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis. • Soliqua 100/33 is not recommended for use in combination with any other product containing a GLP-1 receptor agonist. • Soliqua 100/33 is not indicated for use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. • Soliqua 100/33 has not been studied in patients with gastroparesis and is not recommended in patients with gastroparesis. • Soliqua 100/33 has not been studied in combination with prandial insulin.
Xultophy Xultophy 100/3.6 is a combination of insulin degludec and liraglutide and is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use: • Xultophy 100/3.6 is not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise because of the uncertain relevance of the rodent C-cell tumor findings to humans. • Xultophy 100/3.6 is not recommended for use in combination with any other product containing liraglutide or another GLP-1 receptor agonist. • Xultophy 100/3.6 is not indicated for use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. • Xultophy 100/3.6 has not been studied in combination with prandial insulin.
INITIAL STEP THERAPY For AMYLIN ANALOGS (SymlinPen): If the patient has filled a prescription for at least a 30-day supply of a rapid-acting insulin or short-acting insulin or pre-mixed insulin [e.g., insulin aspart (Novolog), insulin glulisine (Apidra), insulin lispro (Humalog), insulin regular R (Afrezza, Humulin R, Novolin R)] within the past 120 days under a prescription benefit administered by CVS Caremark, then the requested drug will be paid under that prescription benefit. If the patient does not meet the initial step therapy criteria, then the claim will reject with a message indicating that a prior authorization (PA) is required. The prior authorization criteria would then be applied to requests submitted for evaluation to the PA unit.
INITIAL STEP THERAPY For ALL OTHER TARGET DRUGS: If the patient has filled a prescription for at least a 30-day supply of metformin within the past 180 days under a prescription benefit administered by CVS Caremark, then the requested drug will be paid under that prescription benefit. If the patient does not meet the initial step therapy criteria, then the claim will reject with a message indicating that a prior authorization (PA) is required. The prior authorization criteria would then be applied to requests submitted for evaluation to the PA unit.
COVERAGE CRITERIA The requested drug will be covered with prior authorization when the following criteria are met: • The patient has a diagnosis of type 2 diabetes mellitus AND º The patient has NOT been receiving a stable maintenance dose of the requested drug for at least 3 months AND • The patient experienced an inadequate treatment response, intolerance, or has a contraindication to metformin OR • The patient requires combination therapy AND has an A1C of 7.5 percent or greater OR • The request is for Farxiga (dapagliflozin), Invokana (canagliflozin), Jardiance (empagliflozin), Ozempic (semaglutide), Trulicity (dulaglutide), or Victoza (liraglutide) AND the patient has established cardiovascular disease OR • The request is for Invokana (canagliflozin) AND the patient has diabetic nephropathy with albuminuria greater than 300 mg per day OR • The request is for Trulicity (dulaglutide) or Farxiga (dapagliflozin) AND the patient has multiple cardiovascular risk factors OR • The request is for Farxiga (dapagliflozin) or Jardiance (empagliflozin) AND º The patient has a diagnosis of heart failure OR • The request is for Farxiga (dapagliflozin) or Jardiance (empagliflozin) AND º The patient has chronic kidney disease at risk of progression OR º The patient has been receiving a stable maintenance dose of the requested drug for at least 3 months AND • The patient has demonstrated a reduction in A1C since starting this therapy OR • The request is for Farxiga (dapagliflozin), Invokana (canagliflozin), Jardiance (empagliflozin), Ozempic (semaglutide), Trulicity (dulaglutide), or Victoza (liraglutide) AND the patient has established cardiovascular disease OR • The request is for Invokana (canagliflozin) AND the patient has diabetic nephropathy with albuminuria greater than 300 mg per day OR • The request is for Trulicity (dulaglutide) or Farxiga (dapagliflozin) AND the patient has multiple cardiovascular risk factors OR • The request is for Farxiga (dapagliflozin) or Jardiance (empagliflozin) AND º The patient has a diagnosis of heart failure OR • The request is for Farxiga (dapagliflozin) or Jardiance (empagliflozin) AND º The patient has chronic kidney disease at risk of progression OR • The request is for SymlinPen (pramlintide acetate) AND the patient has a diagnosis of type 1 or type 2 diabetes mellitus AND º The patient has NOT been receiving a stable maintenance dose of the requested drug for at least 3 months AND • The patient has failed to achieve desired glucose control despite receiving optimal insulin therapy, including mealtime insulin OR º The patient has been receiving a stable maintenance dose of the requested drug for at least 3 months AND • The patient has demonstrated a reduction in A1C since starting this therapy OR • The request is for Farxiga (dapagliflozin) AND º The patient has a diagnosis of heart failure OR º The patient has chronic kidney disease at risk of progression OR • The request is for Jardiance (empagliflozin) AND º The patient has a diagnosis of heart failure OR º The patient has chronic kidney disease at risk of progression
Duration of Approval (DOA): • DOA: 676-D: 36 months
Place of Service:
Outpatient
The above policy is based on the following references:
Adlyxin [package insert]. Bridgewater, NJ: sanofi-aventis U.S. LLC; June 2022.
Brenzavvy [package insert]. Marlborough, MA: TherascoBio, LLC.; January 2023.
Bydureon BCise [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; December 2022.
Byetta [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; December 2022.
Farxiga [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; May 2023.
Blonde L, Umpierrez GE, Reddy SS et. al. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan – 2022 Update. Endocrine Practice 28 (2022) 923-1049.
Davies MJ, Aroda VR, Collins BS, et. al. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2022;45(11):2753-2786.
El Sayed NA, Aleppo G, Aroda VR et. al. American Diabetes Association, Standards of Care in Diabetes – 2023. Diabetes Care 2023;46(Suppl. 1):S1-S291.
Heidenreich PA, Bozkurt B, Aguilar D et. al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79:e263-e421.
Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.
