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
- Design
- Randomized trial · Surrogate outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationINDIRECT: all participants had obesity or overweight with a weight-related complication, and prediabetes; the analysis is restricted to adherent participants with ≥5% weight reduction.
- Could weight loss explain it?
- Not applicableNot applicable: the outcomes are weight nadir and weight regain themselves, so whether weight loss explains them is not a separate question; no mediation analysis was reported.
- Study tier
- Study tier 3LOW: a post hoc, descriptive subset of one RCT, selected on adherence and response, with no comparator, no CIs and no analysed number in the abstract.
- Assessment
- Version 4 · Two reviewers differed; settled by a recorded ruling · Oct 19, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
This post hoc analysis of the SURMOUNT-1 trial looked only at people with obesity or overweight and prediabetes who stayed on tirzepatide and lost at least 5% of their weight. After their lowest weight, 70% had regained less than 5% by Week 176, 22% had regained 5 to <10% and 8% had regained 10% or more; over 90% moved from prediabetes to normal blood sugar regardless of regain. There is no placebo comparison in this analysis, so it describes treated responders rather than a drug effect.
01Findings
What the study reported
- Drugs
- Tirzepatide
- Dose
- 5 mg, 10 mg, and 15 mg
- Comparator
- none in this analysis (tirzepatide-treated participants only; the parent trial was placebo-controlled)
- Treatment duration
- 3 years
- Primary outcome
- weight regain from weight nadir to Week 176
- Effect
- mean regain from nadir 3.8 kg, 4.4 kg and 3.7 kg (5, 10, 15 mg); pooled doses: 70% <5% regain, 22% 5 to <10%, 8% ≥10%; over 90% converted from prediabetes to normoglycemia regardless of regain
- 95% confidence interval
- not reported in abstract
- Follow-up
- to Week 176
- Adverse events
- not reported in abstract
- Limitations
- A post hoc, descriptive analysis restricted to adherent tirzepatide participants with at least 5% weight reduction, so randomisation does not protect it and there is no placebo comparison; the analysed number is not given.
Who was studied
- Obesity status
- required (obesity or overweight, with at least one weight-related complication)
- Diabetes status
- not reported in abstract (prediabetes required for this analysis)
- Cvd status
- not reported in abstract
- Ckd status
- not reported in abstract
- Baseline condition
- obesity or overweight with prediabetes
- Inclusion exclusion
- tirzepatide-adherent (≥75% of doses received), obesity or overweight with prediabetes at randomization, ≥5% weight reduction from baseline at nadir
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- not extracted
- Randomization
- yes
- Blinding
- double-blind
- Comparator
- none in this analysis (tirzepatide-treated participants only; the parent trial was placebo-controlled)
- Follow up duration
- to Week 176
- Outcome type
- surrogate
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- INDIRECT
- Statistical precision
- no CI reported; analysed number not stated
- Risk of bias
- not assessed
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- not stated in source
- Sponsor role
- not reported in abstract
- Author conflicts
- not reported in abstract
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[OBJECTIVE] For adults with obesity, fluctuations in body weight are expected to occur during weight management. Weight nadirs, which can become a point of focus for people living with obesity, are often hard to maintain. This study aimed to investigate the not well-defined clinical relevance of weight nadir, especially during long-term treatment with an obesity medication. [METHODS] 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. 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. Weight regain analyses from weight nadir to Week 176 included mean percent change, and participants were grouped as having <5%, 5% to <10%, and ≥10% weight regain. [RESULTS] In this post hoc analysis, the mean weight regain from nadir weight to Week 176 was 3.8 kg, 4.4 kg, and 3.7 kg for those treated with tirzepatide 5 mg, 10 mg, and 15 mg, respectively. 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. The median percent of weight reduction maintenance from time of weight nadir to Week 176 was 94.8%, 69.9%, and 44.3%, for <5%, 5-<10%, and ≥10%, respectively. While at baseline 94% of tirzepatide-treated participants had high waist-to-height ratio (WHtR) (>0.59), at week 176 this had reduced to 45%, 59%, and 68% in the <5%, 5% to <10%, and ≥10% weight regain groups, respectively. At Week 176, conversion from prediabetes to normoglycemia occurred in over 90% of tirzepatide-treated participants regardless of weight regain. [CONCLUSION] These findings suggest that most tirzepatide-treated participants with baseline prediabetes in the SURMOUNT-1 3-year study had limited weight regain after reaching weight nadir and sustained improvements in glycemia (SURMOUNT-1 ClinicalTrials.gov identifier: NCT04184622.). [CLINICAL RELEVANCE] In the current study, 92% of prediabetes participants treated with tirzepatide in the SURMOUNT-1 3-year study had a stable weight journey. Their limited weight regain from weight nadir appears not to be clinically meaningful, as improvements in cardiometabolic risk parameters were largely maintained.