TIRZEPATIDE FOR WEIGHT-LOSS MAINTENANCE
SURMOUNT-MAINTAIN supports ongoing Zepbound for weight-loss maintenance
Straight Healthcare
May 2026
May 2026
A common question from patients who have reached their weight-loss goal on Zepbound (tirzepatide) is what happens next. Prior data from the SURMOUNT-4 trial showed that most patients who discontinued tirzepatide after 36 weeks regained most of the weight they had lost. Given these findings, other options are needed.
To compare several maintenance-phase options, researchers conducted the SURMOUNT-MAINTAIN trial (N=378), a 112-week, double-blind, placebo-controlled trial comparing two tirzepatide doses to placebo. Participants first completed a 60-week open-label weight-loss period on once-weekly tirzepatide at the maximum tolerated dose (10 or 15 mg), achieving a mean weight loss of approximately 20% before randomization. They were then re-randomized 3:3:2 to continue the maximum tolerated dose, reduce to tirzepatide 5 mg once weekly, or switch to placebo for 52 weeks. Rescue tirzepatide was available from week 84 onward if weight regain exceeded 50% of the loss achieved during the initial period. The primary endpoint was the percent change in body weight from baseline to week 112. Results were as follows: continue maximum dose −21.9%, reduce to 5 mg −16.6%, placebo −9.9% (estimated treatment difference vs placebo: −12.0% for maximum dose and −6.6% for 5 mg; p<0.0001 for both). Rescue therapy was needed in 8% of the maximum-dose group, 25% of the 5-mg group, and 67% of the placebo group. Gastrointestinal side effects were the most common adverse events and were mostly mild to moderate.
These results provide providers with concrete data to share with patients during the maintenance phase of tirzepatide therapy. Continuing at the maximum tolerated dose preserved the most weight loss, but reducing to 5 mg may be a practical middle ground for patients who find the higher dose difficult to tolerate or afford, keeping in mind that individual responses will vary. Study limitations include US-only enrollment, a predominantly white population, and a roughly two-year follow-up that may not reflect the long-term trajectory. A separate recent trial, ATTAIN-MAINTAIN, found that oral orforglipron (Foundayo) preserved most prior weight loss in patients who had been on injectable tirzepatide or semaglutide and wanted to switch to a daily pill. Together, these studies support ongoing pharmacotherapy — whether injectable or oral — rather than discontinuation for patients who have achieved meaningful weight loss.
To compare several maintenance-phase options, researchers conducted the SURMOUNT-MAINTAIN trial (N=378), a 112-week, double-blind, placebo-controlled trial comparing two tirzepatide doses to placebo. Participants first completed a 60-week open-label weight-loss period on once-weekly tirzepatide at the maximum tolerated dose (10 or 15 mg), achieving a mean weight loss of approximately 20% before randomization. They were then re-randomized 3:3:2 to continue the maximum tolerated dose, reduce to tirzepatide 5 mg once weekly, or switch to placebo for 52 weeks. Rescue tirzepatide was available from week 84 onward if weight regain exceeded 50% of the loss achieved during the initial period. The primary endpoint was the percent change in body weight from baseline to week 112. Results were as follows: continue maximum dose −21.9%, reduce to 5 mg −16.6%, placebo −9.9% (estimated treatment difference vs placebo: −12.0% for maximum dose and −6.6% for 5 mg; p<0.0001 for both). Rescue therapy was needed in 8% of the maximum-dose group, 25% of the 5-mg group, and 67% of the placebo group. Gastrointestinal side effects were the most common adverse events and were mostly mild to moderate.
These results provide providers with concrete data to share with patients during the maintenance phase of tirzepatide therapy. Continuing at the maximum tolerated dose preserved the most weight loss, but reducing to 5 mg may be a practical middle ground for patients who find the higher dose difficult to tolerate or afford, keeping in mind that individual responses will vary. Study limitations include US-only enrollment, a predominantly white population, and a roughly two-year follow-up that may not reflect the long-term trajectory. A separate recent trial, ATTAIN-MAINTAIN, found that oral orforglipron (Foundayo) preserved most prior weight loss in patients who had been on injectable tirzepatide or semaglutide and wanted to switch to a daily pill. Together, these studies support ongoing pharmacotherapy — whether injectable or oral — rather than discontinuation for patients who have achieved meaningful weight loss.
- Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial, Lancet (2026) [PubMed abstract]
- Tirzepatide (Zepbound) review
