What is the discontinuation rate of tirzepatide?

October 11, 2025 •

4 min read

In a real-world study published in June 2025, researchers found that among patients initiating tirzepatide, 16.4% discontinued early (within 3 months) and 34.1% discontinued late (3-12 months). Understanding what is the discontinuation rate of tirzepatide is vital for patients and healthcare providers to effectively manage treatment and expectations.

Quick Summary

Discontinuation rates for tirzepatide differ significantly between controlled clinical trials and real-world settings. Key factors influencing discontinuation include gastrointestinal side effects, medication cost, and insurance coverage issues.

Key Points

Variable Discontinuation Rates: Tirzepatide discontinuation rates vary, with controlled clinical trials showing lower rates (e.g., 14-16% in SURMOUNT-1 for obesity) compared to higher rates observed in real-world settings (e.g., ~50% at one year).
Dose-Dependent Adverse Events: Discontinuation due to adverse events (AEs), primarily gastrointestinal side effects like nausea and diarrhea, is dose-dependent, with higher dosages of tirzepatide associated with higher AE-related discontinuation rates.
Cost and Insurance are Major Factors: In real-world use, financial barriers such as high costs and lack of insurance coverage are frequently cited as the primary reasons for discontinuing tirzepatide and other similar medications.
Management Strategies are Crucial: Patient adherence can be improved by employing strategies such as gradual dose escalation, proactive management of side effects with dietary changes, and addressing financial concerns.
Tapering is Recommended for Discontinuation: To prevent potential negative effects like weight regain, a gradual tapering of the medication under medical supervision is recommended rather than abrupt cessation.

Tirzepatide, marketed as Mounjaro for type 2 diabetes and Zepbound for chronic weight management, has shown impressive efficacy in clinical trials. However, a complete understanding of a medication's profile requires examining not only its benefits but also its long-term adherence. The discontinuation rate of tirzepatide is a critical metric influenced by a complex interplay of patient-related, side-effect, and financial factors.

Tirzepatide Discontinuation in Clinical Trials

Clinical trials offer a controlled environment to assess a drug's performance, but discontinuation still occurs. In the SURMOUNT-1 trial for obesity, overall treatment discontinuation rates were 14.3% (5 mg), 16.4% (10 mg), and 15.1% (15 mg), compared to 26.4% for placebo. The completion rates for tirzepatide arms were notably higher than placebo.

In the SURPASS-1 trial for type 2 diabetes, the rates of discontinuation specifically due to adverse events (AEs) were 6.0% (5 mg), 8.4% (10 mg), and 10.8% (15 mg), significantly higher than the 2.5% in the placebo group. These figures highlight a clear dose-dependent relationship between tirzepatide dosage and AE-related discontinuation. A 2024 meta-analysis confirmed that AE-related discontinuation is higher with tirzepatide than with insulin and with higher doses of tirzepatide compared to other GLP-1RAs. The most common AEs leading to withdrawal were gastrointestinal in nature.

Real-World vs. Clinical Trial Discontinuation

Discontinuation rates reported in real-world studies often exceed those from controlled trials. This discrepancy is due to several variables that are not typically controlled in a clinical setting, such as financial considerations and varying adherence levels. A June 2025 real-world study showed that one-year discontinuation rates for patients on tirzepatide for obesity were substantially higher than in trials. This disparity underscores the impact of real-world constraints on treatment adherence.

Key factors influencing real-world discontinuation

Cost and Insurance Coverage: High out-of-pocket costs and restrictive insurance policies are major hurdles for long-term use. A study examining discontinuation reasons for GLP-1 drugs like tirzepatide found that cost and insurance issues were the most common reasons for stopping.
Medication Shortages: Supply chain issues can lead to temporary or prolonged unavailability of the drug, forcing patients to interrupt or stop treatment.
Lower Maintenance Dosages: Patients in real-world settings are more often on lower maintenance dosages compared to trial participants, which can lead to less optimal weight loss and potentially contribute to dissatisfaction and discontinuation.

Comparison with Semaglutide Discontinuation

Tirzepatide is often compared to semaglutide, another popular GLP-1 receptor agonist. A head-to-head trial in 2025 showed that AE-related discontinuation was lower for tirzepatide (3%) than for semaglutide (6%) at maximal tolerated doses. However, a real-world study from the same year noted overall discontinuation rates were influenced by a wider range of factors, such as cost and adherence.


Feature	Tirzepatide (Clinical Trial)	Semaglutide (Clinical Trial)	Tirzepatide (Real-World)	Semaglutide (Real-World)
Max Dose AE-related Discontinuation	~10.8% (SURPASS-1)	High rates reported in NMAs	Higher than trials, often due to cost/side effects	Higher than trials, often due to cost/side effects
Primary Reason for Discontinuation	GI Adverse Events	GI Adverse Events	Cost, insurance, side effects	Cost, insurance, side effects
Overall Discontinuation	14-16% (SURMOUNT-1)	Varies by trial, often higher in real-world	Higher than trial rates (~50% 1-year)	Higher than trial rates (~50% 1-year)

Strategies to Minimize Discontinuation

Healthcare providers and patients can employ several strategies to mitigate the risk of discontinuation and improve treatment adherence.

Gradual Dose Escalation: As gastrointestinal side effects are often dose-dependent, starting at the lowest dose and escalating slowly allows the body to adjust, which can help improve tolerability.
Managing Gastrointestinal Side Effects: Patients can manage nausea, diarrhea, and constipation through dietary adjustments (e.g., smaller meals, avoiding fatty foods), staying hydrated, and using supportive over-the-counter remedies.
Financial Counseling: Providing information on manufacturer savings programs and navigating insurance coverage can help alleviate financial barriers that commonly lead to discontinuation.
Tapering Off Safely: When discontinuation is necessary, healthcare providers should guide patients on a gradual tapering schedule rather than abrupt cessation. This helps minimize potential side effects and mitigate weight regain.

Practical tips for managing side effects

For Nausea: Eat slowly, have smaller, more frequent meals, and avoid strong-smelling or greasy foods. Consider consuming ginger or peppermint to soothe the stomach.
For Diarrhea: Stay well-hydrated, temporarily avoid high-fiber foods and dairy, and maintain consistent mealtimes.
For Constipation: Gradually increase dietary fiber and fluid intake. Gentle physical activity like walking can also help with digestion.
For Low Blood Sugar (if combined with other diabetes drugs): Be aware of symptoms and carry a source of fast-acting sugar. Discuss dosage adjustments with your doctor if necessary.

Conclusion

The discontinuation rate of tirzepatide is a multifaceted issue, with rates varying significantly between controlled clinical trials and real-world clinical practice. While efficacy is high in trials, real-world adherence is frequently challenged by factors such as gastrointestinal side effects, cost, and insurance limitations. Understanding these differences allows for more realistic patient expectations and targeted management strategies. By employing a "start low, go slow" dose escalation approach, proactively managing side effects, and addressing cost concerns, healthcare providers and patients can work together to improve treatment adherence and achieve sustained therapeutic benefits. Discontinuation, if required, should be a planned process involving a gradual taper under medical supervision to minimize negative outcomes, such as weight regain. For more information on managing side effects, patients can consult their healthcare provider or reference resources from organizations like the NIH on related medication topics.

Frequently Asked Questions

The most common side effects of tirzepatide that lead to discontinuation are gastrointestinal issues, including nausea, vomiting, diarrhea, and constipation. These effects are often most pronounced during dose escalation.

Real-world studies have shown significantly higher discontinuation rates for tirzepatide compared to controlled clinical trials. Factors like cost, insurance coverage, and medication shortages play a much larger role in real-world practice.

Yes, clinical trials indicate a dose-dependent relationship. Higher dosages of tirzepatide, such as 15 mg, have a higher rate of adverse event-related discontinuation than lower doses, though these side effects are often temporary.

You should not stop taking tirzepatide abruptly. Consult with your healthcare provider to create a tapering plan, which involves gradually reducing the dose over several weeks to minimize side effects and reduce the risk of weight regain.

Yes, weight regain is common after discontinuing tirzepatide, especially if healthy lifestyle habits are not maintained. The medication's effect on appetite and metabolism ceases when stopped, and your body's old patterns may return.

Yes. Strategies include starting with a lower dose and escalating slowly, eating smaller and more frequent meals, avoiding fatty foods, staying hydrated, and using remedies like ginger or peppermint for nausea.

In a head-to-head trial comparing max doses, tirzepatide had a lower AE-related discontinuation rate than semaglutide. However, overall real-world rates are affected by various patient-specific factors for both medications.