When to stop GLP-1 (Glucagon-like peptide-1) receptor agonists, such as liraglutide (Victoza) or semaglutide (Ozempic), for weight loss in a patient with obesity?

When to Stop GLP-1 Receptor Agonists for Weight Loss

GLP-1 receptor agonists should generally not be stopped after achieving weight loss goals, as discontinuation leads to rapid and substantial weight regain—patients regain 50-67% of lost weight within one year, regardless of lifestyle interventions. 1, 2, 3

The Evidence Against Stopping Treatment

Weight Regain After Discontinuation

• After stopping semaglutide or tirzepatide, patients regain an average of 9.69 kg (95% CI 5.78-13.60 kg), while liraglutide users regain 2.20 kg (95% CI 1.69-2.70 kg) 3
• Significant weight regain occurs after cessation of semaglutide, with 11.6% of lost weight regained after 52 weeks 1
• The proportion of weight regained is directly proportional to the amount originally lost—meaning those who lost the most weight will regain the most 2, 3
• This weight rebound occurs rapidly and substantially mitigates all metabolic benefits attained through weight loss 2

Loss of Cardiometabolic Benefits

• Stopping semaglutide results in losing the 20% reduction in cardiovascular death, nonfatal MI, or nonfatal stroke that the medication provides 1
• Cardiometabolic improvements including beneficial effects on blood pressure, lipid profiles, and glucose metabolism will reverse with weight regain 1
• Improvements in inflammatory markers like C-reactive protein are lost after stopping 1

When Discontinuation May Be Considered

Inadequate Response (The Only Clear Endpoint)

Discontinue if weight loss is <5% after 3 months at maximum tolerated therapeutic dose 1, 4

• For liraglutide specifically: discontinue if <4% body weight loss after 16 weeks at maintenance dose 4
• In pediatric patients: discontinue if BMI or BMI z-score reduction is <4% after 12 weeks at maximum dose 4
• Early non-responders are unlikely to benefit from continued therapy 4

Safety or Tolerability Issues

Discontinue immediately if:

• Signs of pancreatitis develop (persistent severe abdominal pain) 1
• Signs of gallbladder disease emerge (right upper abdominal pain, fever, jaundice) 1, 4
• Significant safety or tolerability issues occur at any time 1

Pre-Surgical Requirements

• For non-diabetic patients: discontinue semaglutide/tirzepatide for at least 3 weeks (three half-lives) before elective surgery requiring anesthesia due to aspiration risk 1
• For liraglutide: discontinue 3 days before surgery 1
• For diabetic patients: consultation with endocrinology is necessary to weigh risks and benefits of holding medication 1

Strategies If Discontinuation Is Absolutely Necessary

Gradual Tapering Approach

If discontinuation is unavoidable, taper gradually rather than stopping abruptly 1

• Attempt gradual dose reduction to find the minimum dose that maintains weight loss 1
• Reduce by one dose level and monitor for 3 months 1
• This approach may reduce costs and side effects but carries risk of weight regain 1

Intensive Lifestyle Intervention

• Intensify lifestyle interventions immediately upon discontinuation 1
• Combine with a 500-kcal reduction below daily requirements 1
• Maintain minimum 150 minutes/week of physical activity 1
• Include resistance training to preserve lean body mass 1, 4

Close Monitoring Protocol

• Establish monthly weight monitoring for the first 6 months after discontinuation 1
• If weight regain occurs despite ongoing therapy, consider increasing to maximum approved doses 1
• Consider adding structured lifestyle management programs 1
• Evaluate metabolic surgery if BMI ≥30 kg/m² and medical management is insufficient 1

The Lifelong Treatment Paradigm

Why Chronic Therapy Is Necessary

Patients should be counseled that anti-obesity medications must be used lifelong and work best when combined with lifestyle modifications 1

• These medications require lifelong use for sustained weight loss 1, 4
• Sudden discontinuation results in regain of one-half to two-thirds of lost weight within 1 year 1
• GLP-1 RAs should be considered chronic therapy to prevent weight regain and associated undesirable outcomes related to obesity 3

Maintenance Strategy After Achieving Goals

Continue the current therapeutic dose that achieved weight loss goal indefinitely 1

• Monitor quarterly for weight stability, cardiovascular risk factors, and medication tolerance 1
• Assess patients at least every 3 months for continued weight loss progress, cardiovascular risk factors, and medication adherence 1, 4
• Use shared decision-making to determine the best long-term approach 1

Alternative Maintenance Options (With Caution)

Three potential strategies exist, listed from most to least recommended:

1. Maintain full-dose therapy (preferred approach) 1
2. Gradual dose reduction to find minimum effective dose—carries moderate risk of weight regain 1
3. Stopping medication with close monitoring—carries highest risk of treatment failure and requires monthly weight monitoring and strong patient commitment to lifestyle interventions 1

Cost Considerations

• Medication costs approximately $1,272-$1,619 per 30-day supply, requiring long-term financial planning 1
• Payors should cover evidence-based obesity treatments to reduce barriers to treatment access 1
• High discontinuation rates (20-50%) within the first year in real-world settings are often driven by cost and insurance coverage issues 5

Common Pitfalls to Avoid

• Do not stop GLP-1 RAs simply because the patient has reached their weight loss goal—this is not an endpoint but rather the beginning of maintenance therapy 1, 2, 3
• Do not assume lifestyle interventions alone will prevent weight regain after stopping—evidence shows weight regain occurs regardless of lifestyle interventions 2, 3
• Do not delay restarting therapy if weight regain occurs—early intervention is critical 1
• Do not use lower doses than evaluated in clinical trials without close monitoring—real-world evidence shows suboptimal dosing leads to inferior outcomes 5