What are the side effects of Zepbound (tirzepatide)?

From the Guidelines

Zepbound (tirzepatide) is associated with several side effects, including gastrointestinal symptoms, decreased appetite, and injection site reactions, but its benefits in weight loss and potential cardiovascular risk reduction make it a valuable treatment option for patients with obesity or overweight with related comorbidities.

Common Side Effects

• Gastrointestinal side effects: nausea, vomiting, diarrhea, and constipation, especially when starting treatment or increasing doses
• Decreased appetite
• Abdominal pain
• Indigestion
• Fatigue
• Injection site reactions

Less Common but Serious Side Effects

• Pancreatitis
• Gallbladder problems
• Hypoglycemia (particularly when used with insulin or insulin secretagogues)
• Kidney problems
• Allergic reactions
• Potential thyroid tumors (based on animal studies)

Management of Side Effects

Side effects often improve over time as the body adjusts to the medication, and using a gradual dose escalation schedule helps minimize these effects. If you experience severe or persistent side effects while taking Zepbound, contact your healthcare provider immediately rather than discontinuing the medication abruptly, as noted in the 2025 standards of care in diabetes 1.

Benefits of Zepbound

The SURMOUNT-1 trial showed a dose-dependent weight-loss benefit with tirzepatide, a combined glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist, compared with placebo in obese adults without diabetes over 72 weeks 1. This significant weight loss can lead to improvements in cardiovascular risk factors and quality of life. Some patients experience significant weight loss, which is actually the intended effect for those prescribed Zepbound for weight management, as seen in the SURMOUNT-1 trial 1. It is essential to weigh the benefits of Zepbound against its potential side effects and to closely monitor patients for any adverse reactions, as recommended in the 2025 standards of care in diabetes 1.

From the Research

Zepbound (Tirzepatide) Side Effects

• Common side effects of Tirzepatide include:
  • Nausea 2, 3, 4
  • Vomiting 2, 3, 4
  • Diarrhea 3, 4
  • Decreased appetite 3, 4
  • Constipation 3, 4
  • Dyspepsia 4
• More severe side effects include:
  • Pancreatitis 2, 5, 6
  • Cholelithiasis 2, 6
  • Thyroid cancer 2
  • Cholecystitis 2, 6
  • Appendicitis 2
• The incidence of gastrointestinal side effects is positively correlated with the dose of Tirzepatide 3
• The risk of pancreatitis is not significantly associated with Tirzepatide compared to control groups 6
• The composite of gallbladder or biliary disease is significantly associated with Tirzepatide compared to placebo or basal insulin 6

Gastrointestinal Adverse Events

• A meta-analysis showed that total gastrointestinal adverse events, nausea, decreased appetite, constipation, and vomiting were significantly higher in all dose groups of Tirzepatide compared to placebo 3
• Trials sequential analysis showed that the differences in total gastrointestinal adverse events, nausea, decreased appetite, and constipation were conclusive 3
• The gastrointestinal adverse events of Tirzepatide were significantly higher than those of placebo and insulin, but comparable to GLP-1 RA 3

Safety Issues

• A systematic review and meta-analysis found that Tirzepatide appears to be safe regarding the risk of pancreatitis, but the increased risk of the composite outcome of gallbladder or biliary diseases warrants further attention from physicians in clinical practice 6