Tirzepatide · research summary

Evaluation of clinical relevance of weight nadirs and weight regain during 3 years of treatment with tirzepatide in participants with obesity or overweight and prediabetes.

Obesity pillars · 2026. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Post hoc analysis of a phase 3, double-blind, randomized, placebo-controlled clinical trial
“This was a post hoc analysis of the phase 3, double-blind, randomized, placebo-controlled SURMOUNT-1 3-year clinical trial in participants with obesity or overweight and at least one weight-related complication.”

Subjects

Adults with obesity or overweight and prediabetes who were adherent to tirzepatide treatment
“The analysis included participants who were tirzepatide-adherent (≥75% of doses received) with obesity, or overweight, and prediabetes at randomization and had ≥5% weight reduction from baseline at time of weight nadir.”

Sample size

690 tirzepatide-adherent participants
“This post hoc analysis of the SURMOUNT-1 3-year study included 690 tirzepatide-adherent participants (≥75% of doses received) who had ≥5% weight reduction at time of weight nadir.”

Duration

176 weeks (approximately 3 years)
“Participants with prediabetes were followed for 176 weeks, followed by a 17-week off-treatment period.”

Reported findings

Most participants experienced limited weight regain from nadir, with 70% having less than 5% regain
“For the pooled tirzepatide doses, 70% of participants had <5% weight regain, 22% of participants had 5 to <10% weight regain, and 8% of participants had ≥10% weight regain.”
Over 90% of participants achieved normoglycemia at Week 176 regardless of the degree of weight regain
“At Week 176, conversion from prediabetes to normoglycemia occurred in over 90% of tirzepatide-treated participants regardless of weight regain.”
Weight regain of 10% or more was associated with attenuation of earlier benefits in waist-to-height ratio and blood pressure
“While benefits in lipids and glycemia were sustained despite a 10% or more weight increase, there was an attenuation of the earlier benefits in WHtR and blood pressure at the end of study.”

Limitations stated by the authors

The study was post hoc, had a limited sample size in the highest weight regain group, and only included participants with prediabetes
“Other limitations include the post hoc nature of the study and the sample size, especially in the ≥10% weight regain group, and only participants with prediabetes were included in the SURMOUNT-1 3-year study, therefore, this analysis.”

Source: PubMed 42831032 · DOI 10.1016/j.obpill.2026.100333 · all study summaries

Study type

Post hoc analysis of a phase 3, double-blind, randomized, placebo-controlled clinical trial

“This was a post hoc analysis of the phase 3, double-blind, randomized, placebo-controlled SURMOUNT-1 3-year clinical trial in participants with obesity or overweight and at least one weight-related complication.”

Subjects

Adults with obesity or overweight and prediabetes who were adherent to tirzepatide treatment

“The analysis included participants who were tirzepatide-adherent (≥75% of doses received) with obesity, or overweight, and prediabetes at randomization and had ≥5% weight reduction from baseline at time of weight nadir.”

Reported findings

Most participants experienced limited weight regain from nadir, with 70% having less than 5% regain

“For the pooled tirzepatide doses, 70% of participants had <5% weight regain, 22% of participants had 5 to <10% weight regain, and 8% of participants had ≥10% weight regain.”

Over 90% of participants achieved normoglycemia at Week 176 regardless of the degree of weight regain

“At Week 176, conversion from prediabetes to normoglycemia occurred in over 90% of tirzepatide-treated participants regardless of weight regain.”

Weight regain of 10% or more was associated with attenuation of earlier benefits in waist-to-height ratio and blood pressure

“While benefits in lipids and glycemia were sustained despite a 10% or more weight increase, there was an attenuation of the earlier benefits in WHtR and blood pressure at the end of study.”

Limitations stated by the authors

The study was post hoc, had a limited sample size in the highest weight regain group, and only included participants with prediabetes

“Other limitations include the post hoc nature of the study and the sample size, especially in the ≥10% weight regain group, and only participants with prediabetes were included in the SURMOUNT-1 3-year study, therefore, this analysis.”