The SURMOUNT-3 and SURMOUNT-4 studies answer the crucial question: what happens long-term with tirzepatide?
One of the main challenges of anti-obesity treatments is long-term weight loss maintenance. The SURMOUNT-3 and SURMOUNT-4 studies, published in 2023 and 2024, provide essential data on the durability of results with tirzepatide. These studies complete the clinical picture by answering two fundamental questions: can initial weight loss be amplified? And what happens when treatment is stopped?
SURMOUNT-3: Tirzepatide after an intensive lifestyle program
SURMOUNT-3 tested an original approach: what happens if tirzepatide is added to patients who have already lost weight through an intensive lifestyle program (hypocaloric diet and exercise)? The study recruited 579 adults with obesity who had first followed a 12-week intensive program with a very low-calorie diet (meal replacement at 1,000 kcal/day).
After these 12 weeks of run-in, participants had already lost an average of 5.9% of their body weight. They were then randomized to receive maximum dose tirzepatide (15 mg) or placebo for an additional 72 weeks.
The results are impressive. At 72 weeks, the tirzepatide group lost an additional 18.4% (for a total loss of 24.3% since the start of the program), while the placebo group regained weight (+2.5%). This demonstrates that tirzepatide not only consolidates weight loss achieved through lifestyle changes but significantly amplifies it.
SURMOUNT-4: The key study on treatment maintenance and discontinuation
SURMOUNT-4, published in JAMA in 2024, is probably the most important study in the program for patients and clinicians. Its design is unique: all participants (783 adults) received maximum dose tirzepatide for 36 weeks in an open-label phase. Those who had lost at least 5% of their weight (88% of participants) were then randomized to either continue tirzepatide or switch to placebo for an additional 52 weeks.
At week 36 (end of the open-label phase), the average weight loss was 20.9%. Subsequently:
- Continuation group: additional weight loss of 5.5%, reaching 25.3% total loss at 88 weeks
- Discontinuation group (placebo): regained 14% of body weight, bringing the total loss to approximately 9.9%
These results reveal two major insights. Firstly, continuing treatment allows for continued weight loss beyond the first 9 months. Secondly, stopping treatment leads to significant weight regain, although patients remain on average 10% below their initial weight — a non-negligible residual benefit.
Understanding weight regain after discontinuation
Weight regain after tirzepatide discontinuation is not a treatment failure but reflects the chronic nature of obesity. The body has powerful biological mechanisms (increase in ghrelin, reduction in leptin, metabolic adaptation) that favor a return to previous weight. These mechanisms are why obesity should be treated as a chronic disease, similar to diabetes or hypertension.
Nevertheless, SURMOUNT-4 offers a note of hope: patients who maintain a healthy lifestyle after discontinuation (regular exercise, balanced diet) regain less weight than those who return to their previous habits. Treatment could thus serve as a “springboard” to embed lasting changes.
Implications for treatment duration
These two studies have direct implications for treatment recommendations. The majority of obesity experts now recommend long-term treatment for patients with severe obesity or metabolic comorbidities. Discontinuation should only be considered in specific circumstances: weight goal achieved with well-established lifestyle changes, intolerable side effects, or patient preference after informed discussion.
Regular follow-up during and after treatment is crucial. The MounjaGO app allows for long-term weight tracking and early detection of regain, enabling rapid intervention.
FAQ: Weight Loss Maintenance
Should Mounjaro be taken for life?
Not necessarily, but the majority of patients require long-term treatment to maintain benefits. The decision is individual and should be discussed with your doctor, considering your goals, treatment response, and ability to maintain lifestyle changes.
Is all lost weight regained if treatment is stopped?
No. SURMOUNT-4 shows that 52 weeks after discontinuation, patients retain approximately half of the weight loss achieved (residual loss of ~10%). Patients who maintain regular physical activity and a balanced diet regain less.
Can tirzepatide be restarted after a break?
Yes, it is possible to restart treatment after an interruption. Progressive titration should be resumed to minimize gastrointestinal side effects. Discuss this option with your doctor if you notice significant weight regain.