How to safely discontinue Glucagon-like peptide-1 (GLP-1) receptor agonists after achieving weight loss?

How to Stop a GLP-1 After Weight Loss

GLP-1 receptor agonists should generally be continued long-term after weight loss, as discontinuation leads to significant weight regain proportional to the amount lost—patients regaining 2.20 kg after liraglutide and 9.69 kg after semaglutide/tirzepatide cessation. 1

The Weight Regain Problem

When you stop GLP-1 therapy after achieving weight loss, expect substantial weight regain regardless of lifestyle interventions:

• Liraglutide discontinuation: Average weight regain of 2.20 kg (95% CI 1.69-2.70 kg) 1
• Semaglutide/tirzepatide discontinuation: Average weight regain of 9.69 kg (95% CI 5.78-13.60 kg) 1
• Weight regain is proportional to original weight loss achieved 1
• This occurs even with continued lifestyle modifications 2, 1

If Discontinuation Is Necessary

For Patients Using GLP-1 for Weight Loss Only

Simply stop the medication—no tapering is required. 3 However, understand these consequences:

• Weight regain begins immediately after cessation 2, 1
• Body fat percentage increases back toward baseline 2
• Fewer patients maintain ≥10% weight loss one year after stopping compared to those who continue 2

For Patients with Type 2 Diabetes

Do not stop without alternative glucose-lowering therapy in place:

• Ensure alternative diabetes medication is started before stopping GLP-1 3
• Consult endocrinology regarding transition plan 4, 3
• Monitor glycemic control closely after discontinuation 3
• No tapering needed—transition directly to alternative therapy at time of GLP-1 cessation 3

Perioperative Discontinuation (Temporary)

If stopping for surgery, follow this specific protocol:

Timing of Discontinuation

Hold GLP-1 for at least 3 half-lives before the procedure (clears ~88% of drug): 4, 3, 5

• Semaglutide (Wegovy/Ozempic): Hold for 3 weeks (7-day half-life) 5
• Dulaglutide (Trulicity): Hold for 2 weeks (4.5-4.7 day half-life) 5
• Liraglutide (Victoza/Saxenda): Hold for 39 hours (13-hour half-life) 5
• Exenatide (Byetta): Hold for 7.2 hours (2.4-hour half-life) 5

For Diabetes Patients Undergoing Surgery

• Consult endocrinology about bridging with alternative diabetes therapy during the cessation period 4, 3
• Consider risks/benefits of holding for 3 half-lives versus continuing for glycemic control 3
• Continuing closer to surgery may provide benefits in perioperative glycemic control and decreased postoperative cardiac events 3

Resuming After Surgery

Resume GLP-1 therapy after surgery once:

• Patient tolerating oral intake 4
• No ongoing nausea/vomiting 4
• Surgical recovery permits 4

The 2025 multidisciplinary consensus actually recommends continuing GLP-1 throughout the perioperative period with appropriate aspiration risk mitigation strategies rather than routine discontinuation 4, though the 3 half-life rule remains widely cited for high-risk procedures 4, 3, 5.

Strategies to Minimize Weight Regain

Combining Exercise with GLP-1 Before Stopping

Adding supervised exercise to GLP-1 therapy before discontinuation improves weight maintenance:

• Participants who received combined exercise + liraglutide maintained -5.1 kg weight loss one year after stopping both interventions 2
• 7.2 times more likely to maintain ≥10% weight loss compared to those who received placebo 2
• 4.2 times more likely to maintain ≥10% weight loss compared to liraglutide alone 2
• Exercise alone (without GLP-1) also maintained weight better than liraglutide alone after discontinuation 2

The Reality Check

• Weight regain after GLP-1 discontinuation occurs toward pre-treatment body weight 6
• Real-world discontinuation rates are high (20-50% within first year) due to side effects and cost 7
• GLP-1 therapy should be considered chronic treatment to prevent weight regain 1

Common Pitfalls to Avoid

• Don't assume lifestyle changes alone will maintain weight loss after stopping—the evidence shows significant regain regardless 1
• Don't taper the dose—this has no evidence base and only prolongs the inevitable weight regain 3
• Don't stop GLP-1 in diabetic patients without replacement therapy—this risks hyperglycemia and loss of glycemic control 3
• Don't restart at full dose after surgical discontinuation—resume at the maintenance dose the patient was taking 4