Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial.

Garvey WT, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, Jódar E, Kandler K, Rigas G, Wadden TA, Wharton S

Nature medicine10 Oct 2022Cited by 672 (Europe PMC)

PMID36216945PMCIDPMC9556320DOI10.1038/s41591-022-02026-4PepBankPUB-36216945

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Summary

The STEP 5 trial assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) for long-term treatment of adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes. The co-primary endpoints were the percentage change in body weight and achievement of weight loss of ≥5% at week 104. Efficacy was assessed among all randomized participants regardless of treatment discontinuation or rescue intervention. From 5 October 2018 to 1 February 2019, 304 participants were randomly assigned to semaglutide 2.4 mg (n = 152) or placebo (n = 152), 92.8% of whom completed the trial (attended the end-of-trial safety visit). Most participants were female (236 (77.6%)) and white (283 (93.1%)), with a mean (s.d.) age of 47.3 (11.0) years, body mass index of 38.5 (6.9) kg m^-2 and weight of 106.0 (22.0) kg. The mean change in body weight from baseline to week 104 was -15.2% in the semaglutide group (n = 152) versus -2.6% with placebo (n = 152), for an estimated treatment difference of -12.6 %-points (95% confidence interval, -15.3 to -9.8; P < 0.0001). More participants in the semaglutide group than in the placebo group achieved weight loss ≥5% from baseline at week 104 (77.1% versus 34.4%; P < 0.0001). Gastrointestinal adverse events, mostly mild-to-moderate, were reported more often with semaglutide than with placebo (82.2% versus 53.9%). In summary, in adults with overweight (with at least one weight-related comorbidity) or obesity, semaglutide treatment led to substantial, sustained weight loss over 104 weeks versus placebo. NCT03693430.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

3 results from studies that gave the peptide. 3 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with obesity or overweight without diabetes, semaglutide 2.4 mg reduced body weight by 15.2% versus 2.6% with placebo at week 104.
In plain wordsIn adults with obesity or overweight without diabetes, semaglutide lost more body weight than placebo over two years.
Peptide
Semaglutide
Outcome
DecreaseBody weight change at week 104
Study
n = 304
Comparator
Placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
2.4 mg once weekly · subcutaneous · 104 weeksAs given in this study (human).
Measurements
Body weight change
−15.2%
semaglutide 2.4 mg
Body weight change
−2.6%
placebo
Estimated treatment difference
−12.6 %-points
semaglutide vs placebo
Source sentences
Summary
The mean change in body weight from baseline to week 104 was -15.2% in the semaglutide group (n = 152) versus -2.6% with placebo (n = 152), for an estimated treatment difference of -12.6 %-points (95% confidence interval, -15.3 to -9.8; P < 0.0001).
2 context sentences(design, population, supporting numbers)
Summary · context
The STEP 5 trial assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) for long-term treatment of adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes.
Summary · context
From 5 October 2018 to 1 February 2019, 304 participants were randomly assigned to semaglutide 2.4 mg (n = 152) or placebo (n = 152), 92.8% of whom completed the trial (attended the end-of-trial safety visit).
Show in the study text Report a problemFND-3621694501
02HumanRandomized controlled trialEfficacy outcome
In adults with obesity or overweight without diabetes, more participants on semaglutide 2.4 mg than on placebo achieved weight loss of 5% or more at week 104 (77.1% versus 34.4%).
In plain wordsIn adults with obesity or overweight without diabetes, more people on semaglutide than on placebo lost at least 5% of body weight over two years.
Peptide
Semaglutide
Outcome
IncreaseWeight loss of 5% or more at week 104
Study
n = 304
Comparator
Placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
2.4 mg once weekly · subcutaneous · 104 weeksAs given in this study (human).
Measurements
Participants with weight loss >=5%
77.1%
semaglutide 2.4 mg
Participants with weight loss >=5%
34.4%
placebo
Source sentences
Summary
More participants in the semaglutide group than in the placebo group achieved weight loss ≥5% from baseline at week 104 (77.1% versus 34.4%; P < 0.0001).
2 context sentences(design, population, supporting numbers)
Summary · context
The STEP 5 trial assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) for long-term treatment of adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes.
Summary · context
From 5 October 2018 to 1 February 2019, 304 participants were randomly assigned to semaglutide 2.4 mg (n = 152) or placebo (n = 152), 92.8% of whom completed the trial (attended the end-of-trial safety visit).
Show in the study text Report a problemFND-3621694502
03HumanRandomized controlled trialSafety outcome
In adults with obesity or overweight without diabetes, gastrointestinal adverse events were reported more often with semaglutide 2.4 mg than with placebo (82.2% versus 53.9%), mostly mild to moderate.
In plain wordsIn adults with obesity or overweight without diabetes, stomach and gut side effects were more common with semaglutide than with placebo, mostly mild to moderate.
Peptide
Semaglutide
Outcome
IncreaseGastrointestinal adverse events
Study
n = 304
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
2.4 mg once weekly · subcutaneous · 104 weeksAs given in this study (human).
Measurements
Gastrointestinal adverse events
82.2%
semaglutide 2.4 mg
Gastrointestinal adverse events
53.9%
placebo
Source sentences
Summary
Gastrointestinal adverse events, mostly mild-to-moderate, were reported more often with semaglutide than with placebo (82.2% versus 53.9%).
2 context sentences(design, population, supporting numbers)
Summary · context
The STEP 5 trial assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) for long-term treatment of adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes.
Summary · context
From 5 October 2018 to 1 February 2019, 304 participants were randomly assigned to semaglutide 2.4 mg (n = 152) or placebo (n = 152), 92.8% of whom completed the trial (attended the end-of-trial safety visit).
Show in the study text Report a problemFND-3621694503

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 · 1 ongoing · 1 not yet recruiting · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

Not yet recruitingPhase 4NCT07462663

SHAPE-ENDO: Pilot Randomized Trial of Multimodal Pre-Surgical Optimization Versus Standard Surgery in Patients With Obesity and Early-Stage Endometrial Cancer

Hospital Universitari de Bellvitgen = 80est. Jan 2027 to est. Jan 2035

Endometrial Cancer · Endometrial Cancer Stage I · Atypical Endometrial Hyperplasia and Endometrial Carcinoma Stage I · Atypical Endometrial Hyperplasia · Endometrial Intraepithelial Neoplasia · Obesity & Overweight · BMI>40 · Obesity · Obesity Grade III

Trial page ClinicalTrials.govUpdated 10 Jun 2026

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 page ClinicalTrials.govUpdated 6 Apr 2026

CompletedPhase 3Results postedNCT03693430

Two-year Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity

Novo Nordisk A/Sn = 3045 Oct 2018 to 23 Mar 2021

Overweight · Obesity

Trial page ClinicalTrials.govUpdated 6 Jul 2023

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.

Version 2Current
11 Oct 2026, 00:50 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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Terms as the source lists them.

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