Evidence map›Paper›PMID 42348366›Full record

Trial reportDiabetes, obesity & metabolism2026

Tirzepatide Efficacy and Tolerability According to Early Weight Response: A Post Hoc Analysis of the SURMOUNT-1 and SURMOUNT-2 Trials.

Alexander Kokkinos, Tina Thethi, Clare J Lee, Lisa M Neff, Adam Stefanski, Dachuang Cao, Angel Rodriguez, Amy Bartee

2 registry-linked trialsAbstract readRandomized Controlled TrialMulticenter StudyClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT04184622. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04184622 phase3completed

Efficacy and Safety of Tirzepatide Once Weekly in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight- Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-1)

Ran2019Enrolled2,539Registered outcomes26Posted comparisons49ConditionsObesity, OverweightArmsPlacebo, Tirzepatide
Open the trial in the graph
NCT04657003 phase3completed

Efficacy and Safety of Tirzepatide Once Weekly in Participants With Type 2 Diabetes Who Have Obesity or Are Overweight: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-2)

Ran2021Enrolled938Registered outcomes26Posted comparisons41ConditionsObesity, Overweight, Type 2 DiabetesArmsPlacebo, Tirzepatide
Open the trial in the graph
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Trial
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Alexander KokkinosFirst Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
Tina ThethiAdventHealth, Translational Research Institute and AdventHealth Diabetes, Obesity and Endocrinology Institute, Orlando, Florida, USA.ORCID https://orcid.org/0000-0001-6140-906X
Clare J LeeEli Lilly and Company, Indianapolis, Indiana, USA.
Lisa M NeffEli Lilly and Company, Indianapolis, Indiana, USA.
Adam StefanskiEli Lilly and Company, Indianapolis, Indiana, USA.
Dachuang CaoEli Lilly and Company, Indianapolis, Indiana, USA.
Angel RodriguezEli Lilly and Company, Indianapolis, Indiana, USA.ORCID https://orcid.org/0000-0001-8721-9539
Amy BarteeEli Lilly and Company, Indianapolis, Indiana, USA.ORCID https://orcid.org/0009-0005-1355-8331

Funding

Eli Lilly and Company
6 · The paper itself

Abstract

aimsObesity affects over 800 million people globally and is associated with complications including cardiovascular disease and type 2 diabetes (T2D). Early response to weight loss interventions may help optimize achievement of individual treatment goals. Tirzepatide has demonstrated significant weight reduction and improvement in cardiometabolic risk parameters (CRPs) in the SURMOUNT (SM)-1 (NCT04184622) and SM-2 (NCT04657003) trials. We aimed to assess weight reduction, CRPs, tolerability and hypoglycaemia according to early body weight response to tirzepatide in these studies. MATERIALS AND

methodsSM-1 and SM-2 were phase 3, multicentre, randomized, placebo-controlled, double-blind trials evaluating the safety and efficacy of tirzepatide in individuals with obesity or overweight, without (SM-1) or with T2D (SM-2). Post hoc exploratory analyses included tirzepatide-treated participants from SM-1 (n = 1775) and SM-2 (n = 609), categorized as early responders (ERs; ≥ 5% weight reduction) or nonearly responders (non-ERs; < 5% weight reduction) at Week 8. Outcomes were assessed using the efficacy estimand with logistic regression and mixed models for repeated measures.

resultsAcross both studies (N = 2384), ERs were more likely to be female, White and to have lower baseline HbA1c levels. Clinically meaningful weight reduction and improvements in CRPs, including HbA1c, were observed from baseline to Week 72, with significantly greater improvements in ERs compared with non-ERs. The pattern, severity and time course of gastrointestinal events were similar between groups.

conclusionsIn this post hoc analysis of the SURMOUNT-1 and SURMOUNT-2 trials, tirzepatide-treated participants with obesity or overweight in both ER and non-ER groups achieved clinically meaningful weight reduction and improvements in CRPs at Week 72. However, ERs experienced greater weight reduction and improvements in CRP than non-ERs, with a comparable gastrointestinal tolerability profile.

trial registrationSURMOUNT-1: ClinicalTrials.gov: NCT04184622 (https://clinicaltrials.gov/study/NCT04184622). SURMOUNT-2: ClinicalTrials.gov: NCT04657003 (https://clinicaltrials.gov/study/NCT04657003).

Indexed as

Anti-Obesity AgentsDiabetes Mellitus, Type 2ObesityOverweightTirzepatideWeight LossAdultDouble-Blind MethodFemaleHumansMaleMiddle AgedTreatment OutcomeAnti-Obesity AgentsTirzepatideGIPGLP‐1obesity therapyweight management

Identifiers

PMID42348366
PMCPMC13448863

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.