Is Fever a Side Effect of Zepbound? What You Need to Know

Is fever a side effect of Zepbound? Fever is not listed as a common or established side effect of Zepbound (tirzepatide) in FDA prescribing information or clinical trial data. Zepbound, a dual GIP and GLP-1 receptor agonist approved for chronic weight management, primarily causes gastrointestinal side effects such as nausea, diarrhea, and vomiting. While fever may occasionally occur in association with medication-related complications like pancreatitis or injection site infections, it is not a recognized direct effect of the medication. Any fever during Zepbound treatment warrants medical evaluation to determine the underlying cause.

We offer compounded medications and Zepbound®. Compounded medications are prepared by licensed pharmacies and are not FDA-approved. References to Wegovy®, Ozempic®, Rybelsus®, Mounjaro®, or Saxenda®, or other GLP-1 brands, are informational only. Compounded and FDA-approved medications are not interchangeable.

Understanding Zepbound and Its Common Side Effects

Zepbound (tirzepatide) is an FDA-approved prescription medication used for chronic weight management in adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbid condition. It belongs to a class of medications known as dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. Tirzepatide works by mimicking natural hormones that regulate appetite and slow gastric emptying, among other effects. The weight-loss mechanisms are multifactorial and not fully understood.

The most commonly reported side effects of Zepbound are gastrointestinal in nature, with frequency varying by dose. According to the FDA prescribing information, these include:

• Nausea (affecting 24-29% of patients)

• Diarrhea (reported in 18-24% of patients)

• Vomiting (occurring in 8-12% of patients)

• Constipation (affecting 16-17% of patients)

• Abdominal pain or discomfort

• Decreased appetite

• Dyspepsia (indigestion)

• Eructation (belching)

• Gastroesophageal reflux disease

• Alopecia (hair loss)

These gastrointestinal effects are typically most pronounced when initiating therapy or increasing the dose, and often diminish over time as the body adjusts to the medication. The FDA-approved prescribing information recommends gradual dose escalation to minimize these adverse effects.

Other common side effects include injection site reactions (such as redness, swelling, or itching at the injection site) and fatigue. Tolerability often improves with gradual dose escalation, though individual responses vary. Zepbound is not recommended for patients with severe gastrointestinal disease, such as severe gastroparesis. Understanding the expected side effect profile helps patients distinguish between typical medication responses and symptoms that may warrant medical attention.

Is Fever a Known Side Effect of Zepbound?

Fever is not listed as a common or established side effect of Zepbound in the FDA prescribing information or clinical trial data. During the pivotal SURMOUNT clinical trials that led to Zepbound's approval, fever was not reported among the adverse events occurring with notable frequency in patients receiving tirzepatide compared to placebo.

However, it is important to recognize that fever can occasionally occur in association with certain medication-related complications rather than as a direct pharmacological effect. For instance, if a patient develops pancreatitis—a rare but serious potential adverse effect of GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists—fever may be present as part of that clinical syndrome. Similarly, fever could indicate an infection at the injection site (though this is rare) or a systemic infection unrelated to the medication itself.

While some patients may report fever while taking tirzepatide in pharmacovigilance databases, a clear causal relationship has not been established. The temporal association between starting Zepbound and developing fever does not necessarily indicate causation, as many factors can cause fever in any individual.

If you develop a fever (temperature ≥100.4°F or 38.0°C) while taking Zepbound, it is more likely related to:

• A concurrent viral or bacterial infection

• A complication requiring medical evaluation (such as pancreatitis or gallbladder disease)

• Another unrelated medical condition

Patients should not assume that fever is a normal or expected response to Zepbound therapy. Any fever, particularly if accompanied by other concerning symptoms, warrants appropriate medical evaluation to determine the underlying cause.

When to Contact Your Doctor About Fever While Taking Zepbound

While fever is not a recognized side effect of Zepbound, its occurrence during treatment should prompt appropriate clinical assessment. You should contact your healthcare provider if you develop fever (temperature ≥100.4°F or 38.0°C) while taking Zepbound, particularly under the following circumstances:

Call 911 or seek immediate emergency care if fever is accompanied by:

• Severe abdominal pain, especially if persistent and radiating to the back—this may indicate pancreatitis

• Persistent nausea and vomiting that prevents you from keeping down fluids

• Signs of dehydration (decreased urination, extreme thirst, dizziness)

• Yellowing of the skin or eyes (jaundice), which may suggest gallbladder or liver problems

• Severe injection site reactions with spreading redness, warmth, swelling, or pus

• Difficulty breathing or chest pain

• Altered mental status or confusion

Contact your doctor within 24 hours if:

• Fever persists for more than 48 hours without an obvious cause

• You have a temperature above 101°F (38.3°C)

• You experience fever with moderate abdominal discomfort

• You notice unusual symptoms that concern you

Your healthcare provider will need to evaluate whether the fever represents a medication-related complication (such as pancreatitis or cholecystitis), an infection, or an unrelated illness. This assessment typically includes a physical examination, review of symptoms, and potentially laboratory tests or imaging studies.

If pancreatitis is suspected, Zepbound should be discontinued promptly. For other conditions, do not discontinue Zepbound without consulting your healthcare provider, but do report any fever promptly so appropriate evaluation can occur. Early identification of serious complications significantly improves outcomes and allows for timely intervention when necessary.

Other Serious Reactions to Watch for With Zepbound

Beyond fever, several serious adverse reactions associated with Zepbound require immediate medical attention. The FDA prescribing information includes boxed warnings and serious safety concerns that all patients should understand before starting therapy.

Thyroid C-Cell Tumors: Tirzepatide carries a boxed warning regarding the risk of thyroid C-cell tumors, based on animal studies. While this has not been confirmed in humans, Zepbound is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2. Report any neck mass, hoarseness, difficulty swallowing, or shortness of breath immediately.

Acute Pancreatitis: This serious condition has been reported with GLP-1 receptor agonists and tirzepatide. Warning signs include:

• Severe, persistent abdominal pain that may radiate to the back

• Pain that worsens after eating

• Nausea and vomiting

• Abdominal tenderness

If pancreatitis is suspected, Zepbound should be discontinued promptly. If pancreatitis is confirmed, Zepbound should not be restarted.

Gallbladder Disease: Rapid weight loss increases the risk of cholelithiasis (gallstones) and cholecystitis (gallbladder inflammation). Symptoms include right upper abdominal pain, fever, nausea, and jaundice.

Hypoglycemia: When used with insulin or insulin secretagogues, Zepbound may increase hypoglycemia risk. Symptoms include shakiness, sweating, confusion, rapid heartbeat, and dizziness.

Acute Kidney Injury: Dehydration from gastrointestinal side effects may lead to kidney problems. Monitor for decreased urination, swelling, or unusual fatigue.

Severe Allergic Reactions: Though rare, anaphylaxis and angioedema have been reported. Seek emergency care for difficulty breathing, severe rash, or facial swelling.

Diabetic Retinopathy Complications: In patients with diabetes, rapid glucose improvement may temporarily worsen pre-existing diabetic eye disease. While this has been established with some GLP-1 receptor agonists, patients with pre-existing retinopathy should be monitored during tirzepatide treatment.

Pregnancy: Zepbound should be discontinued if pregnancy is recognized due to potential fetal risk.

Zepbound is not recommended for patients with severe gastrointestinal disease, such as severe gastroparesis. Understanding these serious reactions enables prompt recognition and appropriate medical response, optimizing safety during Zepbound therapy.

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