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Study · Randomized controlled trial · n = 327 · 2022

4 results

Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension.

Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, Lingvay I, McGowan BM, Oral TK, Rosenstock J, Wadden TA, Wharton S, Yokote K, Kushner RF

Diabetes, obesity & metabolism19 May 2022Cited by 874 (Europe PMC)

PMID35441470 (opens in a new tab)PMCIDPMC9542252 (opens in a new tab)DOI10.1111/dom.14725 (opens in a new tab)PepBankPUB-35441470
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Summary

AimTo explore changes in body weight and cardiometabolic risk factors after treatment withdrawal in the STEP 1 trial extension.Materials and methodsSTEP 1 (NCT03548935) randomized 1961 adults with a body mass index ≥ 30 kg/m2 (or ≥ 27 kg/m2 with ≥ 1 weight-related co-morbidity) without diabetes to 68 weeks of once-weekly subcutaneous semaglutide 2.4 mg (including 16 weeks of dose escalation) or placebo, as an adjunct to lifestyle intervention. At week 68, treatments (including lifestyle intervention) were discontinued. An off-treatment extension assessed for a further year a representative subset of participants who had completed 68 weeks of treatment. This subset comprised all eligible participants from any site in Canada, Germany and the UK, and sites in the United States and Japan with the highest main phase recruitment. All analyses in the extension were exploratory.ResultsExtension analyses included 327 participants. From week 0 to week 68, mean weight loss was 17.3% (SD: 9.3%) with semaglutide and 2.0% (SD: 6.1%) with placebo. Following treatment withdrawal, semaglutide and placebo participants regained 11.6 (SD: 7.7) and 1.9 (SD: 4.8) percentage points of lost weight, respectively, by week 120, resulting in net losses of 5.6% (SD: 8.9%) and 0.1% (SD: 5.8%), respectively, from week 0 to week 120. Cardiometabolic improvements seen from week 0 to week 68 with semaglutide reverted towards baseline at week 120 for most variables.ConclusionsOne year after withdrawal of once-weekly subcutaneous semaglutide 2.4 mg and lifestyle intervention, participants regained two-thirds of their prior weight loss, with similar changes in cardiometabolic variables. Findings confirm the chronicity of obesity and suggest ongoing treatment is required to maintain improvements in weight and health.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. 4 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    After withdrawal of semaglutide 2.4 mg, participants regained 11.6 percentage points of lost weight by week 120, versus 1.9 after placebo.

    In plain wordsAfter stopping semaglutide, people regained 11.6 percentage points of the weight they lost by week 120, compared with 1.9 after placebo.

    Peptide
    Semaglutide
    Outcome
    IncreaseWeight regained after treatment withdrawal
    Study

    n = 327

    Comparator
    Placebo
    Analysis
    Exploratory
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    2.4 mg once weekly · subcutaneous · 68 weeksAs given in this study (human).

    Measurements

    Weight regained
    11.6 percentage points
    semaglutide, by week 120
    Weight regained
    1.9 percentage points
    placebo, by week 120

    Source sentences

    Summary
    Following treatment withdrawal, semaglutide and placebo participants regained 11.6 (SD: 7.7) and 1.9 (SD: 4.8) percentage points of lost weight, respectively, by week 120
    3 context sentences
    Summary · context
    STEP 1 (NCT03548935) randomized 1961 adults with a body mass index ≥ 30 kg/m2 (or ≥ 27 kg/m2 with ≥ 1 weight-related co-morbidity) without diabetes to 68 weeks of once-weekly subcutaneous semaglutide 2.4 mg (including 16 weeks of dose escalation) or placebo, as an adjunct to lifestyle intervention.
    Summary · context
    An off-treatment extension assessed for a further year a representative subset of participants who had completed 68 weeks of treatment.
    Summary · context
    Extension analyses included 327 participants.
  2. 02HumanRandomized controlled trialEfficacy outcome

    One year after semaglutide withdrawal, net weight loss from week 0 to week 120 was 5.6% with semaglutide and 0.1% with placebo.

    In plain wordsOne year after stopping, people who had taken semaglutide kept a net weight loss of 5.6%, compared with 0.1% after placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseNet weight loss from week 0 to week 120
    Study

    n = 327

    Comparator
    Placebo
    Analysis
    Exploratory
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    2.4 mg once weekly · subcutaneous · 68 weeksAs given in this study (human).

    Measurements

    Net weight loss
    5.6%
    semaglutide, week 0 to 120
    Net weight loss
    0.1%
    placebo, week 0 to 120

    Source sentences

    Summary
    resulting in net losses of 5.6% (SD: 8.9%) and 0.1% (SD: 5.8%), respectively, from week 0 to week 120.
    3 context sentences
    Summary · context
    STEP 1 (NCT03548935) randomized 1961 adults with a body mass index ≥ 30 kg/m2 (or ≥ 27 kg/m2 with ≥ 1 weight-related co-morbidity) without diabetes to 68 weeks of once-weekly subcutaneous semaglutide 2.4 mg (including 16 weeks of dose escalation) or placebo, as an adjunct to lifestyle intervention.
    Summary · context
    An off-treatment extension assessed for a further year a representative subset of participants who had completed 68 weeks of treatment.
    Summary · context
    Extension analyses included 327 participants.
  3. 03HumanRandomized controlled trialEfficacy outcome

    Cardiometabolic improvements seen with semaglutide from week 0 to week 68 reverted towards baseline at week 120 for most variables.

    In plain wordsAfter stopping semaglutide, most heart and metabolic improvements went back towards starting levels by week 120.

    Peptide
    Semaglutide
    Outcome
    MixedCardiometabolic risk factors after withdrawal
    Study

    n = 327

    Comparator
    Placebo
    Analysis
    Exploratory
    Outcome group
    Cardiometabolic risk factors · Metabolic and weight
    Studied dose
    2.4 mg once weekly · subcutaneous · 68 weeksAs given in this study (human).

    Source sentences

    Summary
    Cardiometabolic improvements seen from week 0 to week 68 with semaglutide reverted towards baseline at week 120 for most variables.
    3 context sentences
    Summary · context
    STEP 1 (NCT03548935) randomized 1961 adults with a body mass index ≥ 30 kg/m2 (or ≥ 27 kg/m2 with ≥ 1 weight-related co-morbidity) without diabetes to 68 weeks of once-weekly subcutaneous semaglutide 2.4 mg (including 16 weeks of dose escalation) or placebo, as an adjunct to lifestyle intervention.
    Summary · context
    An off-treatment extension assessed for a further year a representative subset of participants who had completed 68 weeks of treatment.
    Summary · context
    Extension analyses included 327 participants.
  4. 04HumanRandomized controlled trialEfficacy outcome

    In adults with obesity, mean weight loss from week 0 to week 68 was 17.3% with semaglutide 2.4 mg and 2.0% with placebo.

    In plain wordsIn adults with obesity, semaglutide led to 17.3% average weight loss over 68 weeks, compared with 2.0% with placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseMean weight loss from week 0 to week 68
    Study

    n: not reported in source

    Comparator
    Placebo
    Analysis
    Exploratory
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    2.4 mg once weekly · subcutaneous · 68 weeksAs given in this study (human).

    Measurements

    Mean weight loss
    17.3%
    semaglutide, week 0 to 68
    Mean weight loss
    2%
    placebo, week 0 to 68

    Source sentences

    Summary
    From week 0 to week 68, mean weight loss was 17.3% (SD: 9.3%) with semaglutide and 2.0% (SD: 6.1%) with placebo.
    3 context sentences
    Summary · context
    STEP 1 (NCT03548935) randomized 1961 adults with a body mass index ≥ 30 kg/m2 (or ≥ 27 kg/m2 with ≥ 1 weight-related co-morbidity) without diabetes to 68 weeks of once-weekly subcutaneous semaglutide 2.4 mg (including 16 weeks of dose escalation) or placebo, as an adjunct to lifestyle intervention.
    Summary · context
    An off-treatment extension assessed for a further year a representative subset of participants who had completed 68 weeks of treatment.
    Summary · context
    Extension analyses included 327 participants.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials3

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

3 trials · 2 ongoing · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

RecruitingPhase 4NCT07513168

Low-Dose Semaglutide for Weight Loss in Obese Non-Diabetic Pakistani Adults

Asian Institute Of Medical Sciencesn = 601 Aug 2025 to est. 1 Dec 2026

Obesity · Weight Reduction · Cardiometabolic Risk Factors

Trial pageClinicalTrials.govUpdated 6 Apr 2026
RecruitingNot applicableNCT06734312

MAINTAIN (Mucosal AblatIoN Therapy After INcretins)

Dr. Christopher McGowann = 201 Jan 2025 to est. Jun 2026

Obesity and Obesity-related Medical Conditions · Obesity and Overweight · Obesity Prevention · Obesity Recidivism · GLP-1 · Ablation Techniques

Trial pageClinicalTrials.govUpdated 21 Mar 2025
CompletedPhase 3Results postedNCT03548935

STEP 1: Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity

Novo Nordisk A/Sn = 1,9614 Jun 2018 to 5 Mar 2021

Metabolism and Nutrition Disorder · Overweight or Obesity

Trial pageClinicalTrials.govUpdated 19 Nov 2021

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    9 Oct 2026, 18:17 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:06 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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