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Adverse reactions of Tirzepatide

Thyroid C-Cell Tumor Risk

Patients should be informed of the potential risk of medullary thyroid carcinoma (MTC) with the use of tirzepatide, and be advised of symptoms of thyroid tumors (e.g., neck mass, dysphagia, dyspnea, persistent hoarseness). The value of routine monitoring of serum calcitonin or thyroid ultrasound for early detection of MTC in patients treated with tirzepatide is uncertain. Due to the low specificity of serum calcitonin testing and the high baseline incidence of thyroid disease, such monitoring may increase the risk of unnecessary medical procedures. Markedly elevated serum calcitonin levels may suggest MTC, with levels typically >50 ng/L in patients with this cancer. If elevated serum calcitonin is detected, further evaluation of the patient is warranted. Patients with thyroid nodules identified on physical examination or neck imaging also require further evaluation.

Acute Pancreatitis

Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with glucagon-like peptide-1 (GLP-1) receptor agonists or tirzepatide. Patients should be closely monitored for signs and symptoms including persistent or severe abdominal pain (sometimes radiating to the back), with or without nausea and vomiting. If pancreatitis is suspected, tirzepatide should be discontinued immediately and appropriate management should be initiated.

Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin

The concomitant use of tirzepatide with insulin secretagogues (e.g., sulfonylureas) or insulin may increase the risk of hypoglycemia, including severe hypoglycemia. The risk of hypoglycemia can be lowered by reducing the dose of the sulfonylurea (or other concomitant insulin secretagogue) or insulin. Patients using these concomitant medications should be informed of the risk of hypoglycemia and educated on the signs and symptoms of hypoglycemia.

Hypersensitivity Reactions

Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported in patients treated with tirzepatide. If a hypersensitivity reaction occurs, discontinue tirzepatide immediately, provide appropriate treatment per standard clinical practice, and monitor until signs and symptoms resolve. Tirzepatide is contraindicated in patients with a prior serious hypersensitivity reaction to tirzepatide or to any of the excipients in tirzepatide. Caution should be exercised in patients with a history of angioedema or anaphylaxis with a GLP-1 receptor agonist, because it is unknown whether such patients will be predisposed to these reactions with tirzepatide.

Acute Kidney Injury Due to Volume Depletion

Postmarketing reports have shown acute kidney injury, sometimes requiring hemodialysis, in patients treated with GLP-1 receptor agonists or tirzepatide. Most reported cases occurred due to dehydration secondary to gastrointestinal adverse reactions such as nausea, vomiting, and diarrhea. Monitor renal function in patients treated with tirzepatide who experience adverse reactions that may lead to volume depletion, especially during tirzepatide initiation and dose escalation.

Severe Gastrointestinal Adverse Reactions

Tirzepatide may cause gastrointestinal adverse reactions, some of which are severe. In pooled data from placebo-controlled adult trials, the incidence of severe gastrointestinal adverse reactions was higher in tirzepatide groups (1.3% for 5mg, 0.4% for 10mg, 1.2% for 15mg) compared to placebo (0.9%). Severe gastrointestinal adverse reactions have also been reported with GLP-1 receptor agonists in the postmarketing setting. Tirzepatide is not recommended in patients with severe gastroparesis.

Diabetic Retinopathy Complications in Patients with a History of Diabetic Retinopathy

Rapid improvement in blood glucose control may be associated with a temporary worsening of diabetic retinopathy. Tirzepatide has not been studied in patients with non‑proliferative diabetic retinopathy requiring urgent treatment, proliferative diabetic retinopathy, or diabetic macular edema. Patients with a history of diabetic retinopathy should be monitored for progression of retinopathy.

Acute Gallbladder Disease

In placebo-controlled adult trials, acute gallbladder disease was reported in 0.6% of tirzepatide-treated patients and 0% of placebo-treated patients. If cholelithiasis is suspected, appropriate gallbladder diagnostic studies and clinical follow-up are indicated.

Risk of Pulmonary Aspiration During General Anesthesia or Deep Sedation

Tirzepatide delays gastric emptying. Rare postmarketing reports have described pulmonary aspiration in patients receiving GLP-1 receptor agonists who underwent elective surgery or procedures requiring general anesthesia or deep sedation, despite adherence to preoperative fasting requirements. Instruct patients to inform healthcare providers prior to any planned surgery or procedure that they are taking tirzepatide.

Adverse Reactions in Adults

In placebo-controlled clinical trials, the most common adverse reactions (incidence ≥5%) in tirzepatide-treated patients were: nausea, diarrhea, decreased appetite, vomiting, constipation, dyspepsia, and abdominal pain.