Should tirzepatide (glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist) be discontinued in a patient who has attained their goal weight?

Management of Tirzepatide After Reaching Goal Weight

Tirzepatide should be continued long-term at the lowest effective dose even after reaching goal weight, as sudden discontinuation results in regain of one-half to two-thirds of the weight loss within 1 year. 1

Evidence for Continued Therapy

• Sudden discontinuation of tirzepatide leads to substantial weight regain, with studies showing 50-67% of weight being regained within one year after stopping the medication 1, 2
• The 2025 American Diabetes Association Standards of Care explicitly recommends continuing weight management medications long-term unless clinical circumstances (poor tolerance) or other considerations (financial expense, patient preference) suggest otherwise 1
• Weight regain occurs rapidly after cessation of therapy regardless of how long the patient was on treatment, potentially mitigating the metabolic benefits achieved through weight loss 2

Clinical Decision Algorithm

1. For patients who have reached goal weight:

   • Continue tirzepatide at the lowest effective dose that maintains the weight loss 1
   • Schedule follow-up visits at least quarterly to monitor weight maintenance and medication effectiveness 1
   • Consider shared decision-making to determine the optimal long-term approach based on patient preferences and clinical factors 1

2. Options for long-term management include:

   • Continuing full-dose therapy (especially if comorbidities are present) 1, 3
   • Reducing to the lowest effective dose that maintains weight 1
   • Using intermittent therapy (though evidence for this approach is limited) 1
   • Stopping medication with close weight monitoring (high risk of weight regain) 1, 2

Monitoring Recommendations

• After reaching goal weight, continue monitoring at least quarterly 1
• Assess for maintenance of weight loss and potential side effects 1, 4
• Monitor for improvements in comorbid conditions (hypertension, dyslipidemia, glycemic control) 1
• Evaluate the need for adjustment of other medications that may have been prescribed for obesity-related conditions 1

Important Considerations and Pitfalls

• Common pitfall: Discontinuing tirzepatide prematurely after reaching goal weight, which almost invariably leads to significant weight regain 1, 2
• Caution: Patients with renal impairment require careful monitoring when continuing tirzepatide due to potential risk of acute kidney injury 3
• Important: Women of reproductive potential must continue reliable contraception while on tirzepatide, as the medication is contraindicated in pregnancy 1
• Consideration: The financial burden of long-term therapy may influence the decision to continue treatment 1

Special Situations

• For patients who cannot continue tirzepatide due to side effects or cost, intensify lifestyle interventions and consider alternative weight management approaches 1
• For patients with type 2 diabetes who have reached weight goals, continuing tirzepatide provides ongoing glycemic benefits in addition to weight maintenance 5
• For patients who experience gastrointestinal side effects, maintaining the lowest effective dose may improve tolerability while still preventing weight regain 4

Conclusion

The evidence strongly supports continuing tirzepatide long-term after reaching goal weight to prevent weight regain. The decision should involve shared decision-making, considering factors such as comorbidities, medication tolerance, cost, and patient preferences, but the default approach should be continued therapy at the lowest effective dose.