Insulin degludec/liraglutide Disease Interactions

The use of GLP-1 receptor agonists has been associated with rare reports of acute pancreatitis. Other antidiabetic therapies should be considered in patients with a previous history of pancreatitis, although it is not known if they are at increased risk. Patients receiving treatment with GLP-1 receptor agonists should be observed carefully for signs and symptoms of pancreatitis. If this diagnosis is suspected, the treatment should be discontinued immediately and appropriate management should be initiated. Treatment with GLP-1 receptor agonists should be permanently discontinued if pancreatitis is confirmed.

GLP-1 receptor agonist antidiabetic drugs are contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN2). Carcinogenicity studies in rodents and limited postmarketing data suggest that GLP-1 inhibitors may cause a dose-related and treatment duration-related increase in risk of thyroid C-cell tumors, although a causal relationship has not been established.

Therapy with liraglutide should be administered cautiously in patients with depression or any mood or behavior disorder because of the potential for suicidal thoughts or behavior. The drug should be avoided in patients with a history of suicidal attempts or active suicidal ideation.

There have been reports of acute renal failure and worsening of chronic renal failure sometimes requiring hemodialysis in patients treated with GLP-1 receptor inhibitors. Some of these events occurred in patients without known underlying renal disease. These drugs should be used with caution in patients with renal impairment, especially during treatment initiation or dose escalation. Patients should be monitored, especially if they report severe gastrointestinal reactions such as nausea, vomiting, diarrhea, or dehydration. The frequency of gastrointestinal events is increased as renal function declines. There is limited clinical experience with most of these drugs in patients with severe renal impairment.

Insulin requirements may be diminished in patients with renal or hepatic impairment due to reduced insulin metabolism and, in the latter case, also to reduced capacity for gluconeogenesis. Lower initial dosages may be appropriate, with careful monitoring of plasma glucose levels and dosing adjustments.

Hypokalemia may commonly occur during treatment with insulin. Use with caution in patients who may be particularly at risk of developing hypokalemia (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations).

Hypoglycemia may commonly occur during treatment with insulin and/or oral hypoglycemic agents. Care should be taken in patients who may be particularly susceptible to the development of hypoglycemic episodes during the use of these drugs, including those who are debilitated or malnourished, those with defective counterregulatory mechanisms (e.g., autonomic neuropathy and adrenal or pituitary insufficiency), and those receiving beta-adrenergic blocking agents.

Liraglutide can increase the resting heart rate and it should be used with caution in patients with history of cardiovascular disease and cerebrovascular disease. Heart rate should be monitored regularly, and patients should inform their healthcare providers of any symptoms such as palpitations and racing heartbeat appear while at rest.