Semaglutide

Use may be associated with the development of anti-semaglutide antibodies as well as antibodies cross-reacting with native GLP-1. In clinical trials, the percentage of patients developing antibodies to semaglutide and native GLP-1 were 1% and 0.6% respectively.

Use of GLP-1 agonists may increase risk of gallbladder and bile duct disease (Faillie 2016). Cholelithiasis has been reported in patients treated with semaglutide with the majority of patients requiring hospitalization or cholecystectomy; gallbladder studies and further clinical assessment are indicated if cholelithiasis is suspected.

Serious hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported with GLP-1 agonists; permanently discontinue therapy in the event of a hypersensitivity reaction. Use with caution in patients with a history of anaphylaxis or angioedema to other GLP-1 receptor agonists; potential for cross-sensitivity is unknown.

Cases of acute and chronic pancreatitis have been reported; monitor for signs and symptoms of pancreatitis (eg, persistent severe abdominal pain which may radiate to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue use. Do not resume unless an alternative etiology of pancreatitis is confirmed. It is not known if semaglutide increases risk for development of pancreatitis in patients with a history of pancreatitis; consider alternative antidiabetic therapy in these patients.

Acute renal failure and chronic renal failure exacerbation (including severe cases requiring hemodialysis) have been reported; some cases have been reported in patients with no known preexisting renal disease. Reports primarily occurred in patients with nausea, vomiting, diarrhea, or dehydration. Monitor renal function when initiating therapy or increasing doses in patients reporting severe adverse GI reactions.

Dose-dependent and treatment duration-dependent thyroid C-cell tumors have developed in animal studies with semaglutide therapy; it is unknown whether semaglutide will cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined. Patients should be counseled on the potential risk of MTC with the use of semaglutide and informed of symptoms of thyroid tumors (eg, neck mass, dysphagia, dyspnea, persistent hoarseness). Use is contraindicated in patients with a personal or a family history of MTC and in patients with multiple endocrine neoplasia syndrome type 2 (MEN2). Cases of MTC in humans have been reported in patients treated with the GLP-1 receptor agonist liraglutide. Consultation with an endocrinologist is recommended in patients who develop elevated calcitonin concentrations or have thyroid nodules detected during imaging studies or physical exam. Routine monitoring of serum calcitonin or using thyroid ultrasound monitoring is of uncertain value for early detection of MTC in patients treated with semaglutide. Disease-related concerns:

Increased complications associated with diabetic retinopathy have been observed with semaglutide (3%) compared to placebo (1.8%) over a 2-year trial; risk may be increased in patients with a history of diabetic retinopathy at baseline. Monitor for worsening of diabetic retinopathy, particularly in those with a prior history of the disease. Long-term effects of semaglutide on diabetic retinopathy complications are unknown.

Slows gastric emptying; potentially may impact absorption of concomitantly administered oral medication; use caution. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

According to the Centers for Disease Control and Prevention (CDC), pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012). Other warnings/precautions:

Diabetes mellitus: Do not use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis; not a substitute for insulin.

Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.