Lower-dose Zepbound kept most of the weight loss in a Lancet maintenance trial

Adults with obesity who stayed on tirzepatide (Zepbound) at the highest dose they could tolerate kept all of the weight they had lost in a 112-week trial, and those who stepped down to the 5 mg dose kept most of it, according to results published May 12 in The Lancet ^[1][3]. People switched to placebo regained a substantial share of their lost weight ^[1][3].

The trial, called SURMOUNT-MAINTAIN, enrolled 441 adults at 20 US sites ^[1]. They first received open-label tirzepatide for 60 weeks at their maximum tolerated dose of 10 mg or 15 mg ^[1]. Of those, 378 who had lost at least 5% of their body weight and could tolerate the drug were then randomly assigned in a 3:3:2 ratio to continue the maximum tolerated dose (140 people), drop to 5 mg (144 people), or switch to placebo (94 people) for another 52 weeks ^[1][2]. Everyone also received diet and physical activity counseling ^[3]. In all, 345 of 378 (91%) finished the study ^[1].

At the start, participants had a mean body weight of 113.8 kg (about 251 lb), a mean BMI of 40.1, and a mean age of 46.6 years ^[1]. Sixty-five percent were female, and 67% were White ^[1]. The median duration of obesity was 13 years ^[3]. People with type 2 diabetes were not included ^[2].

At week 112, the primary endpoint — percent change in body weight from baseline — was −21.9% for the maximum tolerated dose (95% CI −23.5 to −20.3), −16.6% for the 5 mg dose (95% CI −18.0 to −15.1), and −9.9% for placebo (95% CI −11.1 to −8.8) ^[1][3]. Every comparison with placebo was statistically significant (p<0.0001) ^[1][3]. The estimated treatment difference versus placebo was −12.0% for the maintained dose and −6.6% for 5 mg ^[1]. Lilly's announcement reported the same trial in kilograms, saying people on the maximum tolerated dose lost 25.2 kg (22.4%) and those on 5 mg lost 19.2 kg (17.0%) ^[2]. Those percentages differ slightly from the figures in the journal abstract, and the sources do not explain the difference ^[1][2].

Rescue tirzepatide was offered starting at week 84 — 24 weeks after randomization — to anyone who regained more than half of the weight they had lost ^[1][3]. By that measure, 8% of people on the maximum tolerated dose, 25% on 5 mg, and 67% on placebo received rescue therapy ^[1][3]. In a related announcement the same day, Lilly also reported results from a separate trial, ATTAIN-MAINTAIN, in which people who switched from injectable Wegovy (semaglutide) or Zepbound to the oral drug Foundayo (orforglipron) kept most of their earlier weight loss after a year ^[2].

The most common side effects with tirzepatide were gastrointestinal, mostly mild to moderate, and mostly during dose escalation ^[1]. During the maintenance period, side effects reported more often than with placebo included diarrhea (7.2% on the maximum tolerated dose and 4.9% on 5 mg versus 1.1% on placebo), vomiting (6.5% and 0.7% versus 0%), and nausea (5.8% and 4.2% versus 2.2%) ^[2]. Discontinuation because of side effects during maintenance was 0% on the maximum tolerated dose, 0.7% on 5 mg, and 0% on placebo ^[2]. During the weight-loss period, 20 participants had serious side effects; during maintenance, two people on 5 mg and one on placebo did ^[3].

"Combined, these findings underscore the importance of continued therapy for long-term obesity management and provide evidence for what to expect when reducing the intensity of obesity treatment," wrote Deborah B. Horn, DO, and coauthors ^[3]. In an accompanying editorial, André J. Scheen, MD, wrote that SURMOUNT-MAINTAIN "now provides information on the effect of dose reduction on the maintenance of bodyweight reduction for the first time in a dedicated RCT" ^[3]. The trial was funded by Eli Lilly ^[1][2].

Why it matters for patients

Weight regain after stopping GLP-1 medications has been a central worry for people who take them. This is the first randomized test of lowering the tirzepatide dose instead of stopping, and it found that a reduction to 5 mg kept most of the weight loss over a year ^[1][3].

The only reduced dose tested was 5 mg; nothing lower was studied ^[1]. The results therefore do not speak to microdosing or to compounded versions sold at smaller amounts. The authors also note that individual response can vary and that the findings support ongoing treatment rather than one fixed approach ^[1]. The trial did not include people with type 2 diabetes, so the results may not apply to them ^[2]. Whether these findings change insurance coverage or treatment guidelines has not been reported.

What happens next

The results were presented May 12, 2026, at the 33rd European Congress on Obesity and published the same day in The Lancet ^[2]. A correction notice for the paper appeared in The Lancet on June 6, 2026 ^[1]. Lilly says studies of tirzepatide in chronic kidney disease and in obesity-related illness and death are ongoing; no dates for those results were disclosed ^[2].