Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Moiz A, Levett JY, Filion KB, Peri K, Reynier P, Eisenberg MJ

The American journal of cardiology26 Apr 2024Cited by 65 (Europe PMC)

PMID38679221DOI10.1016/j.amjcard.2024.04.041PepBankPUB-38679221

Publisher page PubMedAsk about this study

Summary

Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated clinically important weight loss effects in patients with type 2 diabetes. However, its effects on sustained weight loss in patients without diabetes remains unclear. Our objective was to examine the long-term efficacy and safety of semaglutide use for weight loss in patients with overweight/obesity and without diabetes. MEDLINE, EMBASE, and the Cochrane Libraries were systematically searched to identify randomized controlled trials that randomized participants with overweight/obesity and without diabetes to once-weekly 2.4 mg subcutaneous semaglutide versus placebo, with a follow-up of at least 68 weeks. The primary outcome was a change in relative body weight from baseline to the longest follow-up. Random-effects models with inverse variance weighting were used to estimate the weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs). A total of 4 randomized controlled trials (n = 3,087) were included. Of the 3 trials that provided body mass index by category (n = 2,783), 94.0% of the participants had a baseline body mass index ≥30 kg/m². Compared with placebo, the use of semaglutide was associated with substantial decreases in long-term relative (WMD -12.1%, 95% CI -13.5 to -10.7) and absolute body weight (WMD -12.3 kg, 95% CI -13.6 to -11.0). At the longest follow-up, 33.4% of participants randomized to semaglutide achieved ≥20% weight loss compared with 2.2% with placebo (RR 15.08, 95% CI 9.31 to 24.43). The risk of gastrointestinal adverse events was higher in participants who took semaglutide than placebo (RR 1:47, 95% CI 1.28 to 1.68); however, the majority of these events were transient and mild-to-moderate in severity and did not require treatment discontinuation. In conclusion, semaglutide is efficacious for sustained weight loss in patients with overweight/obesity and without diabetes.

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

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

01HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity and without diabetes, semaglutide 2.4 mg lowered relative body weight more than placebo at the longest follow-up.
In plain wordsIn adults with overweight or obesity and no diabetes, semaglutide led to more weight loss than placebo over the long term.
Peptide
Semaglutide
Outcome
DecreaseRelative body weight change at longest follow-up
Study
n = 3,087
Comparator
Placebo
Analysis
Primary
Outcome group
Body weight · Metabolic and weight
Studied dose
2.4 mg once weekly · subcutaneous · follow-up of at least 68 weeksAs given in this study (human).
Measurements
Weighted mean difference, relative body weight
−12.1%
semaglutide vs placebo
Source sentences
Summary
Compared with placebo, the use of semaglutide was associated with substantial decreases in long-term relative (WMD -12.1%, 95% CI -13.5 to -10.7)
2 context sentences(design, population, supporting numbers)
Summary · context
MEDLINE, EMBASE, and the Cochrane Libraries were systematically searched to identify randomized controlled trials that randomized participants with overweight/obesity and without diabetes to once-weekly 2.4 mg subcutaneous semaglutide versus placebo, with a follow-up of at least 68 weeks.
Summary · context
A total of 4 randomized controlled trials (n = 3,087) were included.
Show in the study text Report a problemFND-3867922101
02HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity and without diabetes, semaglutide 2.4 mg lowered absolute body weight more than placebo at the longest follow-up.
In plain wordsIn adults with overweight or obesity and no diabetes, semaglutide led to more kilograms of weight loss than placebo over the long term.
Peptide
Semaglutide
Outcome
DecreaseAbsolute body weight change at longest follow-up
Study
n = 3,087
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
2.4 mg once weekly · subcutaneous · follow-up of at least 68 weeksAs given in this study (human).
Measurements
Weighted mean difference, absolute body weight
−12.3 kg
semaglutide vs placebo
Source sentences
Summary
Compared with placebo, the use of semaglutide was associated with substantial decreases in long-term relative (WMD -12.1%, 95% CI -13.5 to -10.7) and absolute body weight (WMD -12.3 kg, 95% CI -13.6 to -11.0)
2 context sentences(design, population, supporting numbers)
Summary · context
MEDLINE, EMBASE, and the Cochrane Libraries were systematically searched to identify randomized controlled trials that randomized participants with overweight/obesity and without diabetes to once-weekly 2.4 mg subcutaneous semaglutide versus placebo, with a follow-up of at least 68 weeks.
Summary · context
A total of 4 randomized controlled trials (n = 3,087) were included.
Show in the study text Report a problemFND-3867922102
03HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity and without diabetes, more participants on semaglutide 2.4 mg than on placebo achieved a weight loss of 20% or more.
In plain wordsIn adults with overweight or obesity and no diabetes, many more people on semaglutide than on placebo lost 20% or more of their weight.
Peptide
Semaglutide
Outcome
IncreaseWeight loss of 20% or more at longest follow-up
Study
n = 3,087
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
2.4 mg once weekly · subcutaneous · follow-up of at least 68 weeksAs given in this study (human).
Measurements
Participants with weight loss of 20% or more
33.4%
semaglutide
Participants with weight loss of 20% or more
2.2%
placebo
Relative risk
15.08 ratio
semaglutide vs placebo
Source sentences
Summary
At the longest follow-up, 33.4% of participants randomized to semaglutide achieved ≥20% weight loss compared with 2.2% with placebo (RR 15.08, 95% CI 9.31 to 24.43).
2 context sentences(design, population, supporting numbers)
Summary · context
MEDLINE, EMBASE, and the Cochrane Libraries were systematically searched to identify randomized controlled trials that randomized participants with overweight/obesity and without diabetes to once-weekly 2.4 mg subcutaneous semaglutide versus placebo, with a follow-up of at least 68 weeks.
Summary · context
A total of 4 randomized controlled trials (n = 3,087) were included.
Show in the study text Report a problemFND-3867922103
04HumanSystematic reviewSafety outcome
In adults with overweight or obesity and without diabetes, the risk of gastrointestinal adverse events was higher with semaglutide 2.4 mg than with placebo.
In plain wordsIn adults with overweight or obesity and no diabetes, stomach and gut side effects were more likely on semaglutide than on placebo.
Peptide
Semaglutide
Outcome
IncreaseGastrointestinal adverse events
Study
n = 3,087
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
2.4 mg once weekly · subcutaneous · follow-up of at least 68 weeksAs given in this study (human).
Source sentences
Summary
The risk of gastrointestinal adverse events was higher in participants who took semaglutide than placebo (RR 1:47, 95% CI 1.28 to 1.68)
2 context sentences(design, population, supporting numbers)
Summary · context
MEDLINE, EMBASE, and the Cochrane Libraries were systematically searched to identify randomized controlled trials that randomized participants with overweight/obesity and without diabetes to once-weekly 2.4 mg subcutaneous semaglutide versus placebo, with a follow-up of at least 68 weeks.
Summary · context
A total of 4 randomized controlled trials (n = 3,087) were included.
Show in the study text Report a problemFND-3867922104
05HumanSystematic reviewSafety outcome
In adults with overweight or obesity and without diabetes, most gastrointestinal events with semaglutide 2.4 mg were transient and mild to moderate.
In plain wordsIn adults with overweight or obesity and no diabetes, most stomach and gut side effects of semaglutide were short and mild to moderate.
Peptide
Semaglutide
Outcome
Not applicableSeverity of gastrointestinal adverse events
Study
n = 3,087
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
2.4 mg once weekly · subcutaneous · follow-up of at least 68 weeksAs given in this study (human).
Source sentences
Summary
the majority of these events were transient and mild-to-moderate in severity and did not require treatment discontinuation.
2 context sentences(design, population, supporting numbers)
Summary · context
MEDLINE, EMBASE, and the Cochrane Libraries were systematically searched to identify randomized controlled trials that randomized participants with overweight/obesity and without diabetes to once-weekly 2.4 mg subcutaneous semaglutide versus placebo, with a follow-up of at least 68 weeks.
Summary · context
A total of 4 randomized controlled trials (n = 3,087) were included.
Show in the study text Report a problemFND-3867922105
06HumanSystematic reviewSafety outcome
In adults with overweight or obesity and without diabetes, most gastrointestinal events with semaglutide 2.4 mg did not require treatment discontinuation.
In plain wordsIn adults with overweight or obesity and no diabetes, most stomach and gut side effects of semaglutide did not make people stop treatment.
Peptide
Semaglutide
Outcome
Not applicableTreatment discontinuation due to gastrointestinal events
Study
n = 3,087
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
2.4 mg once weekly · subcutaneous · follow-up of at least 68 weeksAs given in this study (human).
Source sentences
Summary
the majority of these events were transient and mild-to-moderate in severity and did not require treatment discontinuation.
2 context sentences(design, population, supporting numbers)
Summary · context
MEDLINE, EMBASE, and the Cochrane Libraries were systematically searched to identify randomized controlled trials that randomized participants with overweight/obesity and without diabetes to once-weekly 2.4 mg subcutaneous semaglutide versus placebo, with a follow-up of at least 68 weeks.
Summary · context
A total of 4 randomized controlled trials (n = 3,087) were included.
Show in the study text Report a problemFND-3867922106

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

Registered trials1

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

1 trial · 1 ongoing · 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 page ClinicalTrials.govUpdated 6 Apr 2026

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
9 Oct 2026, 18:17 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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