3-year study of tirzepatide shows that most patients only gain 5% or less from their lowest or ‘nadir’ weight

New research to be presented at this year’s European Congress on Obesity (ECO 2025, Malaga, Spain, 11-14 May) shows that around two thirds of participants of the SURMOUNT-1 trial had only regained 5% or less of their so-called nadir (or lowest weight) three years after beginning treatment with tirzepatide. The study is by Professor Louis Aronne, Comprehensive Weight Control Center, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine, New York, NY, USA, and co-authors from Eli Lilly and Company, Indianapolis, IN, USA, which funded the study.

Obesity management is a long-term journey during which fluctuations in body weight are expected to occur. For some patients, a previous nadir (or lowest) weight can become a point of focus (and disappointment when it cannot be reached again). However, there is not yet clear literature that nadir weight is clinically relevant. This post hoc analysis of the SURMOUNT-1 study, at 3 years, aimed to assess weight regain from nadir weight over 3 years (36 months / 176 weeks) with tirzepatide treatment.

The original SURMOUNT-1 trial was published in NEJM in 2022, and found that, across 72 weeks, participants with obesity treated with 5 mg, 10 mg, or 15 mg of tirzepatide once weekly experienced substantial and sustained reductions in body weight. 

This analysis included 690 tirzepatide-adherent participants (65% female, 35% male) with a mean age of 49 years, a  mean weight of 107 kg, and a mean BMI of 38.6 kg/m² who were chosen from the original SURMOUNT-1 cohort on the basis they had been treatment-adherent across the 3-years (with 75% or more of planned doses received) and were living with obesity(a BMI of at least 30 kg/m²), or overweight (a BMI of at least 27 kg/m²) and prediabetes, and had been participants in the SURMOUNT-1 study and had lost at least 5% of their baseline weight when reaching their nadir weight (the lowest weight achieved during treatment).

Weight regain from nadir to Week 176 was defined as the difference between percent weight reduction from baseline to nadir and percent weight reduction from baseline to Week 176. Weight regain analyses were calculated as a mean across groups and were categorised as less than 5%, 5% to 10%, and 10% or more weight regain.

The analysis showed that the mean time to nadir weight was 22 months (96 weeks). The mean percent weight reduction at nadir weight was 23.1%. The mean percent weight regain from nadir weight to Week 176 was 3.7%, meaning that across the 690 participants over these three years there was a mean percent weight reduction of 19.4% (23.1% minus 3.7%).  

At Week 176, 73%, 19%, and 8% of participants treated with tirzepatide 5 mg (227 participants) regained less than 5%, 5% to 10%, and 10% or more from nadir weight, respectively. Similarly, 65%, 26%, and 9% of participants treated with tirzepatide 10 mg (N=239) regained less than 5%, 5% to 10%, and 10% or more weight from nadir to week 176, respectively. Among participants treated with tirzepatide 15 mg (N=224), 73%, 20%, and 7% experienced less than 5%, 5% to 10%, and 10% or more weight regain from nadir to Week 176, respectively.

The authors have not yet analysed if there are any differences in weight gain between men and women or between older and younger participants.  

Dr Aronne concludes: “This analysis found that 70% of participants treated with tirzepatide had limited weight regain – meaning 5% or less - after their nadir, or lowest weight. Less than 10% of participants regained 10% or more from their nadir weight. Overall, these findings suggest that most participants receiving tirzepatide had a relatively stable weight journey over 3 years in the SURMOUNT-1 3-year study, and managed to avoid any substantial weight regain.”