What are the side effects of Terzepatide (GLP-1 and GIP receptor agonist)?

Tirzepatide Side Effects

Tirzepatide most commonly causes gastrointestinal side effects—particularly nausea, vomiting, and diarrhea—which occur in a dose-dependent manner and are typically mild to moderate and transient. 1

Most Common Side Effects (>10% incidence)

• Gastrointestinal symptoms are the predominant adverse effects, occurring in 39% of patients on 5 mg, 46% on 10 mg, and 49% on 15 mg doses 2
• Nausea and diarrhea are the most frequent GI complaints across all doses 1, 2
• Arthralgia and pain are also common (>10% incidence) according to FDA labeling 3
• Injection site reactions can occur 1

Other Frequent Side Effects

• Vomiting occurs in 2-6% of patients (compared to 2% with placebo) 4
• Constipation has been reported 2
• Esophageal reflux may develop 1
• Elevated heart rate (tachycardia) can be observed and should be monitored, especially in patients with pre-existing cardiovascular conditions 1

Serious Adverse Events (Rare, ≤1%)

• Cholelithiasis and gallstone-related complications including cholecystitis 1, 2
• Acute pancreatitis (extremely rare) 2
• Severe hypoglycemia (particularly when combined with insulin or insulin secretagogues) 1, 2
• Worsening of diabetic retinopathy (though this was specifically noted with semaglutide) 1
• Renal complications in patients with pre-existing kidney disease 1

Black Box Warning

• Thyroid C-cell tumors were observed in rodent studies, leading to a black box warning 1
• Contraindicated in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 1

Dose-Dependent Patterns

• Drug discontinuation due to adverse events increases with dose, reaching 10% at the 15 mg dose 2
• Mild hypoglycemia (blood glucose <70 mg/dL) was highest with the 10 mg dose at 22.6% 2
• GI side effects increase progressively from 5 mg to 15 mg doses 2

Management Strategies

• Start at low dose and titrate slowly to improve tolerability 1
• Reduce meal size to help manage GI symptoms 1
• Limit alcohol and carbonated drinks to reduce reflux 1
• Avoid high-fat diet to help with constipation 1
• Monitor heart rate in all patients, and consider beta-blockers if tachycardia becomes symptomatic 1
• Establish baseline renal function before starting therapy 1
• Monitor for hypoglycemia when used with insulin or insulin secretagogues; lower doses of these medications may be required 1

Special Considerations

• Delayed gastric emptying can affect absorption of other oral medications, particularly those with narrow therapeutic indices like warfarin 1
• Use caution when initiating or increasing doses in patients with kidney disease 1
• Contraindicated in patients with history of serious hypersensitivity reaction to tirzepatide 1
• Use with caution in patients with history of pancreatitis, severe renal impairment, prior gastric surgery, or clinically meaningful gastroparesis 1

Safety Profile Context

• The safety profile is consistent with the GLP-1 receptor agonist class, with GI side effects being the primary concern 5, 4
• No clinically significant or severe hypoglycemia was reported with tirzepatide monotherapy 4
• Fatal adverse events are extremely rare (≤1%) 2