1.1. Adults
Incretin hormones such as glucagon-like peptide (GLP-1) are peptides released from gastrointestinal tract cells in response to food ingestion that stimulate glucose-dependent insulin release from the pancreas, decrease glucagon production, and slow gastric emptying [1]. Incretin mimetics, also known as GLP-1 agonists, are FDA-approved as adjunct therapy to diet and exercise to improve glycemic control in patients with type 2 diabetes [1-8]. GLP-1 agonists are appropriate first-line therapies in patients with type 2 diabetes who have or are at high risk of developing atherosclerotic cardiovascular disease or chronic kidney disease [10 ]. Several GLP-1 agonists have demonstrated cardiovascular benefit in patients with established atherosclerotic cardiovascular disease (ASCVD) including dulaglutide, liraglutide, and the injectable formulation of semaglutide [1,2,5,6]. It is recommended to initiate a GLP-1 agonist with demonstrated cardiovascular benefit, in addition to current therapy, in patients with established ASCVD or indicators of high ASCVD risk including age of 55 years or older with coronary, carotid, or lower extremity artery stenosis greater than 50% or left ventricular hypertrophy.10 Two GLP-1 agonists, Saxenda (liraglutide) and Wegovy (semaglutide), are approved for chronic weight management in patients with a BMI of 30 kg/m2 or greater, or in patients with a BMI of 27 kg/m2 or greater with the presence of at least one weight-related comorbidity, such as hypertension, type 2 diabetes, or dyslipidemia [1,2,7,10]. Wegovy (semaglutide) is also approved to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established cardiovascular disease and either obesity or overweight [1,11,12].
All GLP-1 agonists have been found to cause c-cell tumors in rodent models, but the human relevance has not been determined. All agents except for Byetta (exenatide) have a black box warning for risk of thyroid C-cell tumors, and they are contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC). These agents are also contraindicated in patients with Multiple Endocrine Neoplasia syndrome 2 (MEN 2). Additionally, all GLP-1 agonists have a warning for acute pancreatitis, and patients should not resume therapy with a GLP-1 agonist if acute pancreatitis has occurred. GLP-1 agonists should generally be avoided in patients who are pregnant unless the potential benefit outweighs the potential risk to the fetus. Pregnancy is a contraindication to therapy for the following agents; Saxenda (liraglutide), Wegovy (semaglutide), Rybelsus (semaglutide), and Ozempic (semaglutide) [1-8].
Additional warnings for this drug class include hypoglycemia when used in combination with an insulin secretagogue or insulin, acute kidney injury or renal impairment, and hypersensitivity reactions. GLP-1 agonists have not been studied in patients with gastroparesis, and all drugs within this class, except for liraglutide and semaglutide, recommend against use in patients with preexisting gastroparesis [1-8].
GLP-1 agonist recommended dosages are summarized in Table 1. Patient profiles containing prescriptions with GLP-1 agonist dosages that exceed these recommendations will be reviewed.
| Drug Name | Dosage Form/Strength | Treatment Indications | Maximum Recommended Dosage |
|---|---|---|---|
| dulaglutide (Trulicity) | extended-release SC solution; 0.75 mg/0.5 mL, 1.5 mg/0.5mL, 3 mg/0.5 mL, and 4.5 mg/0.5 mL as single-dose pens | type 2 diabetes mellitus; reduction of CV events | 0.75 mg SC once weekly, then titrate to 1.5 mg once weekly; if glycemic control not achieved, may titrate up every 4 weeks to a maximum of 4.5 mg once weekly |
| exenatide (Byetta) | regular-release SC solution; 5 mcg/0.02 mL pen, 10 mcg/0.04 mL pen* | type 2 diabetes mellitus | 5 mcg SC twice daily initially within 60 minutes prior to the morning and evening meals, or prior to the two main meals of the day spaced six hours or more apart; dose may be increased to 10 mcg twice daily prior to the morning and evening meals (or the two main meals of the day, spaced six hours or more apart) after one month of therapy based on clinical response |
| exenatide (Bydureon BCise | extended-release SC injectable suspension; 2 mg/0.85 mL single dose autoinjector+ | type 2 diabetes mellitus | 2 mg SC once weekly at any time of day, with or without meals |
| liraglutide (Victoza, generic) | SC solution; multi-dose pen (18 mg/3 mL) that delivers doses of 0.6 mg, 1.2 mg, or 1.8 mg | type 2 diabetes mellitus; reduction of CV events | 0.6 mg@ SC daily for at least one week; titrate to 1.2 mg daily, up to maximum of 1.8 mg daily |
| liraglutide (Saxenda) | SC solution; multi-dose pen (18 mg/3 mL) that delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3 mg | chronic weight management | 0.6 mg SC daily for at least one week, followed by an increase in increments of 0.6 mg every week up to maximum of 3 mg SC mg daily |
| semaglutide (Ozempic) | SC solution; multi-dose pen available as either 0.25 mg or 0.5 mg per dose (2 mg/3 mL), 1 mg per dose (4 mg/3 mL), or 2 mg per dose (8 mg/3 mL) | type 2 diabetes mellitus; reduction of CV events | 0.25 mg@ SC once weekly x 4 weeks, then titrate upward to 0.5 mg once weekly; if glycemic control not achieved after 4 weeks, may titrate to 1 mg once weekly; if glycemic control not achieved after 4 weeks, may titrate to a maximum of 2 mg once weekly |
| semaglutide (Wegovy) | SC solution; single-dose pen that delivers doses of 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, or 2.4 mg | chronic weight management; reduction of CV events# | 0.25 mg SC weekly for at least 4 weeks, followed by a dose escalation every 4 weeks up to maximum of 2.4 mg daily |
| tirzepatide (Mounjaro) | SC solution; single dose pens available as 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg per 0.5 mL | type 2 diabetes mellitus | 2.5 mg@ SC once weekly x 4 weeks, then titrate upward to 5 mg SC once weekly; if glycemic control not achieved, may titrate up by 2.5 mg increments every 4 weeks to a maximum of 15 mg SC once weekly |
Legend:
- SC = subcutaneous
- * each exenatide regular-release pen provides 60 doses of medication
- + each exenatide extended-release autoinjector is single-dose; supplied in carton of 4 pens
- # TAC Rule section 354.1923 excludes coverage of these products for obesity control indications
- @ indicates dose is for therapy titration only – does not provide glycemic control
| Drug Name | Dosage Form/Strength | Treatment Indications | Maximum Recommended Dosage |
|---|---|---|---|
| semaglutide (Rybelsus) | 3 mg, 7 mg, 14 mg oral tablets | type 2 diabetes mellitus | 3 mg@ daily for 30 days then titrate up to 7 mg daily, may titrate after 30 days to a maximum of 14 mg daily |