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Once-Weekly Semaglutide in Adults with Overweight or Obesity
Open accessAbstract
BACKGROUND: Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed. METHODS: In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions. RESULTS: The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]). CONCLUSIONS: In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).
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“In subjects with obesity without T2D, 26 weeks of treatment with JNJ-64565111, at the highest tested dose of 10 mg, resulted in a placebo-corrected weight loss of ~10%, relative to −5.8% in liraglutide-treated controls101.”
From Transforming obesity: The advancement of multi-receptor drugs (2024) · cites this paper as [101]
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In the citing paper
“Clinically, GLP-1 RAs are indicated for the treatment of type 2 diabetes (all) and obesity (liraglutide and semaglutide only) and have beneficial effects on patient-important outcomes such as weight loss, cardiovascular and kidney events, hepatic steatosis, and mortality.5,7–9,11,30”
From Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review (2024) · cites this paper as [11]
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In the citing paper
“For semaglutide1, 74.8%, 54.8%, and 34.8% achieved those, while for tirzepatide [4] it was 90.1%, 78.2% and 62.9%.”
From New drugs for the treatment of obesity: do we need approaches to preserve muscle mass? (2025) · cites this paper as [1]
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In the citing paper
“Once weekly semaglutide at a dose of 2.4 mg administered subcutaneously is a potent glucagon-like peptide 1 receptor agonist that is approved for long-term weight management”
From Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity (2023) · cites this paper as [13]
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“In these clinical trials, mean weight loss at 68 weeks was 14.9% (placebo, 2.4%; difference, 12.4%; 95% CI, 11.5%-13.4%) and 16.0% (placebo, 5.7%; difference, 10.3%; 95% CI, 8.6%-12.0%), respectively.81,99”
From Obesity Management in Adults: A Review (2023) · cites this paper as [81]
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In the citing paper
“the well-documented decline in lean mass and BMD associated with that degree of weight loss must be considered.”
From The Benefits of Exercise Training in Combination With Weight Loss Therapies (2025) · cites this paper as [42]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Despite inducing a smaller magnitude of weight loss than tirzepatide, treatment with semaglutide resulted in an even more significant loss of lean mass, of 6.9 kg, or 13.9%, over its 68-week trial period (42).”
From The Benefits of Exercise Training in Combination With Weight Loss Therapies (2025) · cites this paper as [42]
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In the citing paper
“Indeed, clinical trials demonstrate substantial weight loss achievable with GLP1Ra-based therapy, ranging from 12-15% over a one-year period for semaglutide (6), to weight losses rivaling what is seen with bariatric surgery for tirzepatide (7).”
From G LP1Ra ‐based therapies and DXA ‐acquired musculoskeletal health outcomes: a focused meta‐analysis of placebo‐controlled trials (2025) · cites this paper as [6]
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In the citing paper
“Across body weight and composition outcomes, the greatest magnitude of weight loss was observed in the SURMOUNT (7) and STEP (6) trials, respectively.”
From G LP1Ra ‐based therapies and DXA ‐acquired musculoskeletal health outcomes: a focused meta‐analysis of placebo‐controlled trials (2025) · cites this paper as [6]
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In the citing paper
“In the context of a body weight reduction of 14.9% (À15.3 kg) and fat reduction of 24.7% (À10.4 kg), individuals also lost an average of 13.9% of their total LM (À6.9 kg) (17).”
From Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition? (2024) · cites this paper as [17]
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In the citing paper
“As discussed above, Sema administration is associated with an LM loss of 13.9% ($6.9 kg) over a period of 68 weeks (17), while Tz induced a 10.9% (6 kg) loss over 72 weeks of therapy (20).”
From Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition? (2024) · cites this paper as [17]
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In the citing paper
“Regarding fat mass, evidence suggests a decrease of $29% after incretin therapy (17,20)”
From Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition? (2024) · cites this paper as [17]
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In the citing paper
“In addition, most patients’ weight loss plateaus.5,6,13”
From Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity (2025) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In 2021, semaglutide 2.4 mg became the most-effective GLP-1 RA approved for obesity management with 14.9% mean WL at 68 weeks vs. 2.4% with placebo [8].”
From Triple Agonism Based Therapies for Obesity (2025) · cites this paper as [8]
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In the citing paper
“A once-weekly injection of 2.4 mg of semaglutide resulted in a remarkable reduction in body weight by − 14.9% in adults with obesity, along with substantial improvements in glucose homeostasis and reduced risk of cardiovascular events [66, 67].”
From Dual and Triple Incretin-Based Co-agonists: Novel Therapeutics for Obesity and Diabetes (2024) · cites this paper as [67]
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In the citing paper
“Semaglutide 2.4 mg once weekly is the latest approved GLP-1 RA for obesity management (2021) and results in 15–17% mean WL through appetite reduction [11, 12].”
From What is the pipeline for future medications for obesity? (2025) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“As the new obesity pharmacotherapies will lead up to 15–25% mean WL, intensive lifestyle interventions may provide small additional WL benefit to these treatments [11, 106].”
From What is the pipeline for future medications for obesity? (2025) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For the OMM semaglutide, the DXA substudy of the STEP 1 trial of adults with obesity or overweight receiving semaglutide reported an absolute reduction of 10.4 kg total fat mass and 6.9 kg total body lean mass, corresponding to a proportional body weight reduction of 60% fat mass and 40% lean mass.”
From Body composition changes during weight reduction with tirzepatide in the SURMOUNT ‐1 study of adults with obesity or overweight (2025) · cites this paper as [31]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the first of the STEP trials (STEP 1–4), 68 weeks of once-weekly s.c. semaglutide 2.4 mg treatment resulted in mean weight loss of 15%–17% in adults with overweight or obesity and 10% in those who also had type 2 diabetes.13, 14, 15, 16”
From Effects of once-weekly semaglutide 2.4 mg on C-reactive protein in adults with overweight or obesity (STEP 1, 2, and 3): exploratory analyses of three randomised, double-blind, placebo-controlled, phase 3 trials (2023) · cites this paper as [15]
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In the citing paper
“as it is well-known that weight loss has an anti-inflammatory effect [30–32]”
From Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials (2022) · cites this paper as [30]
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In the citing paper
“Semaglutide mimics the effects of endogenous GLP-1, a gut-derived incretin hormone. It acts centrally on hypothalamic GLP-1 receptors to suppress appetite, enhance satiety, and reduce food intake.”
From Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies (2025) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the semaglutide treatment effect in people (STEP) with obesity trials, semaglutide 2.4 mg weekly produced a mean placebo-adjusted weight loss of 14.9% over 68 weeks in STEP 1, and up to 16.0% in STEP 4 with continued use [6,8].”
From Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies (2025) · cites this paper as [6]
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In the citing paper
“Peripherally, it slows gastric emptying and improves insulin secretion in a glucose-dependent manner, indirectly promoting weight loss [6].”
From Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies (2025) · cites this paper as [6]
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In the citing paper
“It is common in obesity pharmacotherapy trials that more people in the placebo group are lost to follow-up than in the active treatment group.8,10,35”
From Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment: a post-treatment analysis of a randomised placebo-controlled trial (2024) · cites this paper as [8]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In an opinion in the Journal of Physiology [209], we have recently argued that the bimagrumab effects in patients with obesity are preferable to those of, e.g., semaglutide because the fat loss is not associated with muscle atrophy, as is the case with semaglutide treatment [210].”
From Effects of Skeletal Muscle Hypertrophy on Fat Mass and Glucose Homeostasis in Humans and Animals: A Narrative Review with Systematic Literature Search (2025) · cites this paper as [210]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“These real‐world pancreatitis rates of approximately 4 to 8 per 1000 person‐years with GLP‐1RA are several fold higher than in the major weight loss RCTs of liraglutide RCT. 17 , 18 , 19 , 26”
From Real‐world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP ‐ 1RA ‐based weight‐loss therapies (2025) · cites this paper as [18]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the recently approved 2.4 mg dose of once-weekly GLP-1R agonist semaglutide (Wegovy) increases mean weight reduction in this population to 15–20% [[5], [6], [7], [8]]”
From Next generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice (2022) · cites this paper as [5]
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In the citing paper
“There is observational data to infer an additive and possibly synergistic effect of exercise with GLP-1R agonism on weight loss, suggesting non-anorectic mechanisms that are not well characterized [5,66].”
From Next generation GLP-1/GIP/glucagon triple agonists normalize body weight in obese mice (2022) · cites this paper as [5]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The findings from three studies (n = 3375) 16 -18 showed that semaglutide induced a more significant enhancement in health-related quality of life compared to placebo. This improvement was evidenced by the higher SF-36 physical functioning score (MD:1.75 [95% CI 0.92, 2.58]; P < 0.0001 [Figure S11]).”
From Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta‐analysis including the 2‐year STEP 5 trial (2024) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Furthermore, four studies (n = 3087) 16,17,19,20 revealed that semaglutide led to a greater percentage of trial discontinuations due to GI AEs relative to placebo (RR 5.36, [95% CI 2.49, 11.55]; P < 0.0001 [Figure S16]).”
From Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta‐analysis including the 2‐year STEP 5 trial (2024) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Four studies (n = 3087) 16,17,19,20 reported a modification in levels of CRP, an indicator of inflammation. Evaluation of the combined analysis showed that semaglutide caused a significant reduction in CRP compared to placebo (MD: 38.92% [95% CI 43.69, 34.16]; P < 0.00001)”
From Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta‐analysis including the 2‐year STEP 5 trial (2024) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This approval was based on the Semaglutide Treatment Effect in People with Obesity (STEP) clinical trial programme, which demonstrated significant weight reduction, improvement of cardiometabolic factors, and positive patient-reported outcomes. 16 -20”
From Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta‐analysis including the 2‐year STEP 5 trial (2024) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the semaglutide groups demonstrated a significant reduction in weight at the end of the treatment period for various steps, namely, 14.9% for STEP 1, 16% for STEP 3, 17.4% for STEP 4, 15.2% for STEP 5, and 15.8% for STEP 8.”
From Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta‐analysis including the 2‐year STEP 5 trial (2024) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The safety profile of AMG 133 was similar to that of GLP-1RAs, including unimolecular GLP-1/GIPR agonist peptides6,7.”
From A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings (2024) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This result is in contrast to observations with GLP-1 RAs, for which increased glucose tolerance and weight loss are observed in adults with obesity following treatment [15].”
From Results from three phase 1 trials of NNC9204-1177, a glucagon/GLP-1 receptor co-agonist: Effects on weight loss and safety in adults with overweight or obesity (2023) · cites this paper as [15]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the STEP 1 trial, 95 participants treated with semaglutide in the DXA subset lost 6.9 kg (~13%) LST alongside 10.4 kg (~25%) FM, 2 corresponding to ~40% of weight loss as LST.”
From Preservation of lean soft tissue during weight loss induced by GLP-1 and GLP-1/GIP receptor agonists: A case series (2025) · cites this paper as [2]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“though lean soft tissue loss comprised 26%–40% of weight loss in recent trials”
From Preservation of lean soft tissue during weight loss induced by GLP-1 and GLP-1/GIP receptor agonists: A case series (2025) · cites this paper as [2]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Several RCTs have demonstrated a significantly higher prevalence of gallbladder disorders among patients treated with GLP-1 RAs compared to placebo [29-32], as initially evidenced by the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, which reported acute gallstone disease rates of 3.1% in the liraglutide group versus 1.9% in the placebo”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [32]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“clinical trials showed that semaglutide and tirzepatide were highly effective for weight reduction”
From Strategies for minimizing muscle loss during use of incretin‐mimetic drugs for treatment of obesity (2025) · cites this paper as [1]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In phase 3 trials, women aged ≥ 65 years achieved sustained weight loss of 10–20%, with consistent cardiometabolic improvements.”
From A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass (2026) · cites this paper as [35]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Despite this attenuation, the improvements observed in metabolic parameters, such as HbA1c (glycated hemoglobin), blood pressure, and lipid profiles, were significant.”
From A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass (2026) · cites this paper as [35]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In both trials, subanalyses specifically focusing on women aged 65 years and older showed that these individuals experienced significant reductions in body weight, comparable to those seen in younger cohorts.”
From A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass (2026) · cites this paper as [35]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Two major trial programs, the STEP program for semaglutide [35,36,37,38,39] and the SURMOUNT trials [40,41,42,43] for tirzepatide, offer critical insights into the benefits of these therapies in older populations.”
From A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass (2026) · cites this paper as [35]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“On average, weight loss in this age group ranged from 10–15%, with a slight attenuation of this effect in participants aged over 70 years.”
From A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass (2026) · cites this paper as [35]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In particular, glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1ra) has demonstrated sustained, clinically significant body weight reductions in patients with T2DM and obesity (1–3).”
From Transforming body composition with semaglutide in adults with obesity and type 2 diabetes mellitus (2024) · cites this paper as [1]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In STEP-1 (semaglutide), lean mass decreased by ~9.7% while fat mass fell by ~19.3%, with the proportion of lean mass increasing by ~3 percentage points (35).”
From GLP-1 agonists and exercise: the future of lifestyle prioritization (2025) · cites this paper as [35]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Although both represent important therapeutic advances, the results obtained with retatrutide suggest potential superiority regarding the magnitude of weight loss, possibly as a result of the additional activation of the glucagon receptors and the consequent increase in energy expenditure”
From RETATRUTIDE USE IN THE TREATMENT OF METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE (MASLD) AND OBESITY: AN INTEGRATIVE REVIEW (2026) · cites this paper as WILDING et al., 2021
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Studies conducted with semaglutide showed relevant weight losses, accompanied by consistent metabolic benefits, while investigations in patients with steatohepatitis demonstrated a significant increase in the rates of resolution of liver disease”
From RETATRUTIDE USE IN THE TREATMENT OF METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE (MASLD) AND OBESITY: AN INTEGRATIVE REVIEW (2026) · cites this paper as WILDING et al., 2021
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Glucagon like peptide-1 receptor agonists (GLP-1RA) are a class of medications that were originally approved for diabetes treatment with the notable side effect of pronounced weight loss.23–25”
From The Effect of Semaglutide and GLP-1 RAs on Risk of Nonarteritic Anterior Ischemic Optic Neuropathy (2025) · cites this paper as [25]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Body composition was assessed using DXA, which is the gold standard for this purpose.”
From Impact of Semaglutide on fat mass, lean mass and muscle function in patients with obesity: The SEMALEAN study (2026) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In STEP 1, semaglutide 2.4 mg OW led to 10–15% Weight loss and restoration of normoglycemia in 84.1% of prediabetic participants over 68 weeks [3].”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In STEP 1, ~ 13.6% of participants on semaglutide 2.4 mg did not meet this threshold despite adherence at week 68 [3].”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In STEP 1, up to 74% of participants reported nausea with semaglutide 2.4 mg, yet discontinuation for GI reasons was relatively low (4.5%) [3].”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [3]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“New and emerging highly effective OMMs, such as tirzepatide and semaglutide, have contributed to major shifts in the practice of obesity care,7 with meaningful reductions in cardiovascular-related endpoints.8–11”
From Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: post-hoc analysis of the SURMOUNT-5 trial (2025) · cites this paper as [8]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“GLP‐1s reduce body weight by 5% to 18% in trials, with modestly lower effects in real‐world analyses, and multiple demonstrated clinical benefits.”
From Nutritional priorities to support GLP ‐1 therapy for obesity: A joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society (2025) · cites this paper as [14]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Generally, weight reduction is more rapid during the first 6 months and slows thereafter, with relative plateauing at 18 months [13, 14, 15].”
From Nutritional priorities to support GLP ‐1 therapy for obesity: A joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society (2025) · cites this paper as [14]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the STEP 1 trial, of the average 13.6‐kg–weight reduction, 8.3 kg (62%) was fat mass and 5.3 kg (38%) was lean body mass (including muscle and other nonfat tissues) [14].”
From Nutritional priorities to support GLP ‐1 therapy for obesity: A joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society (2025) · cites this paper as [14]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In comparison, the STEP 1 trial that included semaglutide with general nutrition and physical activity instructions demonstrated a 14.9% weight reduction from baseline (vs. 2.4% with general nutrition and physical activity instructions alone) [14].”
From Nutritional priorities to support GLP ‐1 therapy for obesity: A joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society (2025) · cites this paper as [14]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Although limited direct evidence has evaluated use of GLP‐1s with or without RDN‐provided MNT, the SCALE [13], STEP 1 [14], SURMOUNT [15], and STEP 3 [178] trials each demonstrated substantial weight reduction by combining GLP‐1s with regular counseling sessions by RDNs or other qualified healthcare professionals”
From Nutritional priorities to support GLP ‐1 therapy for obesity: A joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society (2025) · cites this paper as [14]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Weight loss of 15% or greater can lead to substantial clinical improvements, such as remission of T2D and significant reductions in cardiovascular risk factors [24]”
From Impact of Digital Engagement on Weight Loss Outcomes in Obesity Management Among Individuals Using GLP-1 and Dual GLP-1/GIP Receptor Agonist Therapy: Retrospective Cohort Service Evaluation Study (2025) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Despite the large weight losses with obesity medications, long-term adherence in a real-world setting is challenging since the medications are expensive and gastrointestinal adverse events are common.8,10,11”
From Healthy weight loss maintenance with exercise, GLP-1 receptor agonist, or both combined followed by one year without treatment: a post-treatment analysis of a randomised placebo-controlled trial (2024) · cites this paper as [8]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Although most patients taking a GLP-1 RA achieve clinically meaningful weight loss, heterogeneity in response exists.3,4,5,6,7,12”
From Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity (2025) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“More than 70% of patients in clinical trials of GLP-1 RAs reported adverse events, most often gastrointestinal (GI), that were mild.3,4,5,6,7”
From Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity (2025) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The health benefits seen with continued treatment with the maximum tolerated dose of tirzepatide during this study were achieved with a safety profile consistent with that previously reported in SURMOUNT and SURPASS trials and in studies of incretin-based therapies approved for the treatment of obesity and overweight.18,25,26,27,28,29,30,31,32”
From Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial (2024) · cites this paper as [30]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Third, many RCTs included relatively few people from racial and ethnic minority groups and relatively small proportions of men.81,99”
From Obesity Management in Adults: A Review (2023) · cites this paper as [81]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“pivotal randomized trials of GLP-1 RAs for obesity (STEP, SURMOUNT, SCALE) all incorporated intensive lifestyle interventions modeled on Diabetes Prevention Program-style curricula, and the magnitude of weight loss in the control arms of these trials confirms that structured lifestyle support produces clinically meaningful effects in this population even without GLP-1 RA therapy [9,13,76,77].”
From Adherence and Persistence with GLP-1-Based Therapies: International Real-World Evidence and the Role of Nutritional and Lifestyle Support—A Narrative Review (2026) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The most successful weight-loss trials to date—including the STEP program for semaglutide [9] and the SURMOUNT program for tirzepatide [13]—have incorporated intensive lifestyle interventions as a core component of the trial protocol, modeled on the structured behavioral curricula pioneered by the Diabetes Prevention Program (DPP) [76,77].”
From Adherence and Persistence with GLP-1-Based Therapies: International Real-World Evidence and the Role of Nutritional and Lifestyle Support—A Narrative Review (2026) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“noted superiority over other GLP-1RAs.”
From Semaglutide for the treatment of antipsychotic-associated weight gain in patients not responding to metformin – a case series (2023) · cites this paper as [31]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Regarding the subcutaneous treatments, the EMP for semaglutide was similar to liraglutide, whereas semaglutide has been shown to be more than twice as effective, with a PSWL of À12.7 kg versus À5.6 kg respectively, although this was after a longer treatment course of 68 weeks [10,24,25].”
From Estimated minimum prices and lowest available national prices for antiobesity medications: Improving affordability and access to treatment (2023) · cites this paper as [24]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Results from the STEP 1 trial of semaglutide suggested that 40% of total weight loss was derived from lean mass.42”
From Effectiveness and safety of drugs for obesity (2024) · cites this paper as [42]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Recent studies have shown that pharmacologically assisted weight loss with glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucagon-like peptide-1 receptor (GLP-1R)/ glucose-dependent insulinotropic polypeptide receptor agonists (GIP-RAs) is approaching magnitudes close to that achieved with bariatric surgery.1,39,92”
From Changes in lean body mass with glucagon‐like peptide ‐1‐based therapies and mitigation strategies (2024) · cites this paper as [1]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the STEP-1 trial of semaglutide, lean mass was reduced by À6.92 kg or À 13.2%, with a weight reduction of À15.3 kg or À14.9%, yielding a fraction of weight lost from lean mass of 45.2%. 1”
From Changes in lean body mass with glucagon‐like peptide ‐1‐based therapies and mitigation strategies (2024) · cites this paper as [1]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Semaglutide and tirzepatide have demonstrated weight‐loss efficacy comparable to bariatric surgery, with mean reductions of up to 20.9% in body weight, along with other metabolic benefits, across pivotal trials [1, 2, 3, 4].”
From Nutrition Strategies for Next‐Generation Incretin Therapies: A Systematic Scoping Review of the Current Evidence (2026) · cites this paper as [1]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“To date, most dietary advice during incretin therapy has focused on calorie reduction, with little emphasis on nutritional adequacy [1, 9]”
From Nutrition Strategies for Next‐Generation Incretin Therapies: A Systematic Scoping Review of the Current Evidence (2026) · cites this paper as [1]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This stepwise approach anchored in trial evidence strengthens confidence in the validity and applicability of the current results, reinforcing the role of GLP-1-based therapies beyond previously established benefits in the evolving management of cardiometabolic HFpEF.54,56-62”
From Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction (2025) · cites this paper as [59]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Many patients treated with GLP-1RAs achieve clinically meaningful weight loss while simultaneously demonstrating improvements in cardiometabolic health.45,46”
From Receipt of Glucagon-Like Peptide-1 Receptor Agonists Among Rural Patients with Obstructive Sleep Apnea and Excess Weight (2026) · cites this paper as [45]
The cited source says what the claim attributes to it.
In the citing paper
“an RCT involving the weekly semaglutide showed a 14.9% decrease in body weight after treatment for 68 weeks (42).”
From The Benefits of Exercise Training in Combination With Weight Loss Therapies (2025) · cites this paper as [42]
The cited source says what the claim attributes to it.
In the citing paper
“with two articles presenting LM outcomes in only a subset of participants from the parent trial (6, 7).”
From G LP1Ra ‐based therapies and DXA ‐acquired musculoskeletal health outcomes: a focused meta‐analysis of placebo‐controlled trials (2025) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“However, the magnitude of the treatment effect on total body mass was nearly two times greater in trials using GLP1Ra-based therapies at dosages indicated primarily for chronic weight management (6, 7, 18, 21, 24) as compared to trials using dosages indicated primarily for diabetes management (17, 19, 20, 22): −10.2 kg (−16.3, −3.9) versus −5.5 kg (−8.7, −2.1), respectively.”
From G LP1Ra ‐based therapies and DXA ‐acquired musculoskeletal health outcomes: a focused meta‐analysis of placebo‐controlled trials (2025) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“A subsequent 68-week intervention in middle-aged adults with overweight or obesity using semaglutide (Sema) (2.4 mg) reduced body weight by 14.9% (À15.3 kg) versus 2.4% (À2.6 kg) in the placebo group (17).”
From Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition? (2024) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“These safety findings are similar to those reported for therapies based on GLP-1 or GIP/GLP-1 agonism for the treatment of type 2 diabetes or obesity41–45.”
From Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial (2024) · cites this paper as [43]
The cited source says what the claim attributes to it.
In the citing paper
“Although no data from head-to-head trials comparing retatrutide to other currently approved obesity treatments exist, data from the phase 2 studies with retatrutide suggest that at higher doses, retatrutide could lead to greater WL compared to the most efficacious approved treatments for obesity and T2D such as tirzepatide 15 mg and semaglutide 2.4 mg (Fig. 3) [8, 27, 45, 46, 49, 50].”
From Triple Agonism Based Therapies for Obesity (2025) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“Notably, nearly 50% of the retatrutide phase 2 obesity trial were men, which is higher than in phase 3 clinical trials with tirzepatide (32.5% in SURMOUNT-1 [27]) and semaglutide 2.4 mg (25.9% in STEP-1 [8]).”
From Triple Agonism Based Therapies for Obesity (2025) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“However, the weight loss was less pronounced than the 14.9% weight loss (vs. 2.4% with placebo) seen in the STEP 1 trial in adults with overweight or obesity without diabetes (129).”
The cited source says what the claim attributes to it.
In the citing paper
“The percentages of participants who experienced AE leading to treatment discontinuation as well as of those who experienced gastrointestinal AE with oral semaglutide 50 mg (Tables 2 and 3) were similar to those observed with subcutaneous semaglutide 2.4 mg (in STEP-1 and STEP-2 trials 6–7% discontinued treatment due to AE, 34–44% experienced nausea, 21–32% diarrhoea and 22–25% vomiting) [11, 29].”
From What is the pipeline for future medications for obesity? (2025) · cites this paper as [11]
The cited source says what the claim attributes to it.
In the citing paper
“Semaglutide, a glucagon-like peptide receptor agonist (GLP- 1 RA), was shown in STEP 1 to produce mean weight reduction from baseline to week 68 of − 14.9% for semaglutide versus − 2.4% for placebo, by treatment-policy or treatment-regimen estimand which is reported throughout this manuscript, except where noted [1].”
From New drugs for the treatment of obesity: do we need approaches to preserve muscle mass? (2025) · cites this paper as [1]
The cited source says what the claim attributes to it.
In the citing paper
“has previously been shown to produce major weight loss in persons with overweight or obesity and to have favorable effects on cardiometabolic risk factors. 13,14”
From Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity (2023) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“Semaglutide 2.4 mg, a recently approved selective GLP-1RA for long-term weight management in obese adults, has shown greater effectiveness compared to these earlier AOMs [27].”
The cited source says what the claim attributes to it.
In the citing paper
“The safety profile observed was consistent with findings from other incretin-based therapies, particularly similar to the safety profile of GLP-1RA like liraglutide and semaglutide used for obesity treatment [27, 42].”
The cited source says what the claim attributes to it.
In the citing paper
“Recent advancements in obesity pharmacotherapy, particularly glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, tirzepatide), revolutionized treatment paradigms, demonstrating unprecedented efficacy in clinical trials [6,7].”
From Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies (2025) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“The total weight reduction was approximately similar to the 15% weight loss that was observed after 68 weeks of treatment with the GLP-1 receptor agonist semaglutide, administered subcutaneously at a dose of 2.4 mg once weekly as an adjunct to lifestyle change (currently not approved by any governmental medical agencies at this dose and for this indication). 30”
From Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined (2021) · cites this paper as [30]
The cited source says what the claim attributes to it.
In the citing paper
“In the main phase of the STEP 1 trial, 68 weeks of treatment with semaglutide plus lifestyle intervention in adults with overweight/obesity produced clinically meaningful reductions in body weight, as well as improvements in cardiometabolic risk factors, and physical functioning. 16”
From Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension (2022) · cites this paper as [16]
The cited source says what the claim attributes to it.
In the citing paper
“Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have emerged as key agents for weight management, based on their marked efficacy as observed in randomized controlled trials.”
From Real‐world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP ‐ 1RA ‐based weight‐loss therapies (2025) · cites this paper as [18]
The cited source says what the claim attributes to it.
In the citing paper
“The three GLP‐1RA‐based agents currently approved for weight loss have all shown clear efficacy in promoting weight loss in randomized controlled trials (RCTs), 17 , 18 , 19 that is, in settings with good medication adherence among participants and a follow‐up of typically one to two years. 15”
From Real‐world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP ‐ 1RA ‐based weight‐loss therapies (2025) · cites this paper as [18]
The cited source says what the claim attributes to it.
In the citing paper
“In the STEP 1 trial, 2.4 mg·week−1 of the glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide resulted in 15% mean weight loss over 68 weeks. 2”
From Preservation of lean soft tissue during weight loss induced by GLP-1 and GLP-1/GIP receptor agonists: A case series (2025) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“In the STEP 1 trial, participants completed individualized counseling sessions to promote a 500 kcal·day−1 energy deficit and completion of ⩾150 min·week−1 physical activity. 2”
From Preservation of lean soft tissue during weight loss induced by GLP-1 and GLP-1/GIP receptor agonists: A case series (2025) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“Generally, approximately 15% weight loss was observed in overweight and obese, non-diabetic adults across various treatment periods, lasting up to 2 years (from STEP-1 to STEP-6, STEP-8) [72,73,74,75,76,77,78,79].”
From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [72]
The cited source says what the claim attributes to it.
In the citing paper
“Notably, Wilding et al. highlighted that combining Semaglutide treatment with lifestyle interventions effectively sustained clinically relevant weight loss in overweight or obese adults (1).”
From Transforming body composition with semaglutide in adults with obesity and type 2 diabetes mellitus (2024) · cites this paper as [1]
The cited source says what the claim attributes to it.
In the citing paper
“Clinical studies using DEXA show that GLP-1–based weight loss is accompanied by some loss of lean mass, but fat loss predominates.”
From GLP-1 agonists and exercise: the future of lifestyle prioritization (2025) · cites this paper as [35]
The cited source says what the claim attributes to it.
In the citing paper
“Semaglutide promoted a mean reduction of approximately 14.9% of body weight, while tirzepatide achieved losses close to 20.9%.”
From RETATRUTIDE USE IN THE TREATMENT OF METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE (MASLD) AND OBESITY: AN INTEGRATIVE REVIEW (2026) · cites this paper as WILDING et al., 2021
The cited source says what the claim attributes to it.
In the citing paper
“Few studies have used DXA, 6 , 8 the gold standard for measuring body composition, and even fewer have assessed muscle function. 9 , 10”
From Impact of Semaglutide on fat mass, lean mass and muscle function in patients with obesity: The SEMALEAN study (2026) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“Semaglutide, administered once weekly at a dose of 2.4 mg, has demonstrated significant weight loss outcomes in clinical trials, with reductions in body weight exceeding 15% in many patients. 5 , 6”
From Impact of Semaglutide on fat mass, lean mass and muscle function in patients with obesity: The SEMALEAN study (2026) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“STEP 1 showed 14.9% loss over 68 weeks [3].”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“Both the STEP 1 and SURMOUNT-1 trials, evaluating semaglutide and tirzepatide, respectively, demonstrated clinically meaningful improvements in HRQoL measures as assessed by standardized tools (e.g., IWQOL-Lite, SF-36), even in people without diabetes or established cardiovascular disease [2, 3].”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [3]
The cited source says what the claim attributes to it.
In the citing paper
“The GLP-1 receptor agonist, semaglutide, resulted in 12% larger weight loss than placebo after 68 weeks.8”
The cited source says what the claim attributes to it.
In the citing paper
“Although most patients taking a GLP-1 RA achieve clinically meaningful weight loss, heterogeneity in response exists.3,4,5,6,7,12”
From Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity (2025) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) substantially lower weight,3,4,5,6,7 hemoglobin A1c levels, and cardiovascular risk,8 trials suggest they must be continued for sustained effects.9,10”
From Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity (2025) · cites this paper as [6]
The cited source says what the claim attributes to it.
In the citing paper
“In STEP 1, 68 weeks of treatment with once‐weekly s.c. semaglutide 2.4 mg plus lifestyle intervention provided significant, clinically relevant reductions in body weight versus placebo among adults with overweight/obesity.”
From Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension (2022) · cites this paper as [16]
The cited source says what the claim attributes to it.
In the citing paper
“although this proportion represented a substantial fall from that originally achieved at the end of 68 weeks of treatment (86.4%).”
From Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension (2022) · cites this paper as [16]
The cited source says what the claim attributes to it.
In the citing paper
“While RCTs report retention rates often exceeding 85% over 68 weeks [9]”
The cited source says what the claim attributes to it.
In the citing paper
“The treatment of obesity with semaglutide 2.4 mg presents challenges for both patients and providers, including managing side effects [8], insurance coverage issues [9], and frequent national shortages of the medication [10].”
From A Qualitative Analysis of Patient Experiences Using Semaglutide 2.4 mg for Weight Loss (2025) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“Semaglutide (S/C) [2.4 mg/wk, price calculated for 10.25 mg per 30 days] Treatment À14.9% (À15.3 kg) vs. placebo À2.4% (À2.6 kg) [after 68 weeks] [10, 24]”
From Estimated minimum prices and lowest available national prices for antiobesity medications: Improving affordability and access to treatment (2023) · cites this paper as [24]
The cited source says what the claim attributes to it.
In the citing paper
“Average total weight loss 14.9% at 68 weeks 42”
From Effectiveness and safety of drugs for obesity (2024) · cites this paper as [42]
The cited source says what the claim attributes to it.
In the citing paper
“In STEP-1, weekly semaglutide 2.4 mg led to a mean placebo-adjusted body weight reduction of 12.4% at 68 weeks in adults with obesity, with significant improvements in cardiometabolic risk factors.19”
From The Triple‐Agonist Revolution: Retatrutide and the Paradigm Shift in Multi‐Hormonal Pharmacotherapy for Obesity and Cardiometabolic Comorbidities (2026) · cites this paper as [19]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“A CVOT for naltrexone/bupropion-ER was terminated early, and there was insufficient data to assess CV safety.753”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [753]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The frequency of these side effects occurred in 84% and 67% of subjects receiving JNJ-64565111 and in 71% and 48% of subjects administered liraglutide101.”
From Transforming obesity: The advancement of multi-receptor drugs (2024) · cites this paper as [101]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“In both studies, treatment with JNJ-64565111 resulted in an increased appearance of adverse effects, most notably nausea and vomiting101,102.”
From Transforming obesity: The advancement of multi-receptor drugs (2024) · cites this paper as [101]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Moreover, the magnitude of WL with retatrutide also exceeded that seen with other pipeline multi-agonists such as CagriSema (cagrilintide, an amylin agonist, in combination with semaglutide), mazdutide and survodutide (Fig. 4) [8, 27, 35, 36, 45, 46, 49–53].”
From Triple Agonism Based Therapies for Obesity (2025) · cites this paper as [8]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Semaglutide users can regain two-thirds of their loss within one year off treatment [6].”
From Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies (2025) · cites this paper as [6]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Dual GIP/GLP-1 agonists such as tirzepatide have already demonstrated unprecedented mean weight losses of >20% in the SURMOUNT-1 trial, validating co-agonism as a superior strategy [6].”
From Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies (2025) · cites this paper as [6]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve HFpEF outcomes, 13,14 but have variable and modest effects on health status and exercise function, with resultant significant residual risk. 15-17”
From Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials (2024) · cites this paper as [14]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Semaglutide and tirzepatide initiators appeared to achieve the greatest weight loss in real life, and weight loss effects were weaker for patients with T2D than for obese people without diabetes, 52 , 58 , 65 , 67 which was also observed in trials. 18 , 75”
From Real‐world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP ‐ 1RA ‐based weight‐loss therapies (2025) · cites this paper as [18]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Clinical evidence demonstrated that the combination of these two pathways promotes benefits superior to those observed with isolated GLP-1 agonists, a fact initially evidenced by the results obtained with tirzepatide in the treatment of obesity”
From RETATRUTIDE USE IN THE TREATMENT OF METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE (MASLD) AND OBESITY: AN INTEGRATIVE REVIEW (2026) · cites this paper as WILDING et al., 2021
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Across major trials, women, especially premenopausal, tend to experience greater relative weight loss with GLP-1 RAs and dual incretin therapies such as tirzepatide [2, 3].”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [3]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“However, real-world effectiveness lags trial efficacy, largely owing to high discontinuation rates.”
From Adherence and Persistence with GLP-1-Based Therapies: International Real-World Evidence and the Role of Nutritional and Lifestyle Support—A Narrative Review (2026) · cites this paper as [9]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“For type 2 diabetes, complementary disease-modifying therapies that may reduce or eliminate the need for insulin administration have also represented a rapidly expanding field of interest130–132.”
From 100 years of insulin: celebrating the past, present and future of diabetes therapy (2021) · cites this paper as [132]
Experimental — accuracy not yet measuredIn the citing paper
“semaglutide demonstrated up to 15% mean weight loss (8), sustained over at least two years (9)”
From Regional trends and disparities in newer GLP1 receptor agonist initiation among real‐world adult patients eligible for obesity treatment (2025) · cites this paper as [8]
In the citing paper
“have shown greater effectiveness, health benefits, and safety profiles (7; 8).”
From Regional trends and disparities in newer GLP1 receptor agonist initiation among real‐world adult patients eligible for obesity treatment (2025) · cites this paper as [8]
In the citing paper
“In STEP 1 and 3, participants were randomized 2:1 to escalating doses of semaglutide up to 2.4 mg/week or placebo for 68 weeks as an adjunct to either lifestyle intervention”
In the citing paper
“The STEP 1, 2, 3, and 4 trials demonstrated that semaglutide 2.4 mg compared with placebo, as adjunct to lifestyle management or intensive behavioral therapy, led to mean weight losses of 6–15% in participants with and without type 2 diabetes (14,18–20).”
In the citing paper
“All three trials were conducted according to the International Conference on Harmonisation Good Clinical Practice Guideline and the Declaration of Helsinki; all participants provided written informed consent (14,18,19).”
In the citing paper
“Semaglutide has been shown to lower body weight by up to 16% when used in conjunction with lifestyle recommendations [10, 11, 12, 13].”
From Semaglutide for cardiovascular event reduction in people with overweight or obesity: SELECT study baseline characteristics (2023) · cites this paper as [10]
In the citing paper
“The study uses standard‐of‐care preventive measures along with semaglutide 2.4 mg subcutaneous once‐weekly treatment, which has been demonstrated to provide significant and sustained mean weight loss of up to 16% [10, 11, 12, 13, 24, 25], significant CV risk factor improvements, and proven CV benefit in patients with diabetes and prior CV events [16, 26].”
From Semaglutide for cardiovascular event reduction in people with overweight or obesity: SELECT study baseline characteristics (2023) · cites this paper as [10]
In the citing paper
“In the phase III Semaglutide Treatment Effect in People with obesity (STEP) 1‐4 studies, weekly semaglutide 2.4 mg demonstrated substantial, clinically meaningful weight losses and improvements in cardiometabolic parameters and patient‐reported outcomes.”
In the citing paper
“Contraindicated in patients with personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2 or known hypersensitivity to semaglutide.”
From Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022 (2022) · cites this paper as [43]
In the citing paper
“Semaglutide at 2.4 mg subcutaneously per week is approved for treatment of obesity.”
From Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022 (2022) · cites this paper as [43]
In the citing paper
“Average weight reduction is about 15%.”
From Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022 (2022) · cites this paper as [43]
In the citing paper
“Glucagon-like peptide-1 receptor agonist that at lower injectable doses 0.25–2.0 mg per week, and at oral doses of 7–14 mg per day, is indicated to lower blood sugar in patients with type 2 diabetes mellitus.”
From Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022 (2022) · cites this paper as [43]
In the citing paper
“Semaglutide 2.4 mg subcutaneously once weekly | Overall mean = 15%≥5% = 86%≥10% = 69%≥15% = 51%≥20% = 32%”
From Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022 (2022) · cites this paper as [43]
In the citing paper
“Like other GLP-1R agonists, SMG often causes adverse reactions. The main adverse reactions were gastrointestinal side effects, including nausea, diarrhea, and vomiting. These adverse reactions are generally mild to moderate and gradually alleviated in most patients (100, 104).”
From GLP−1 receptor agonists for the treatment of obesity: Role as a promising approach (2023) · cites this paper as [100]
In the citing paper
“In the STEP1 trial (100), Wilding et al. recruited 1961 non-diabetic adults with a BMI of 30 kg/m2 (or ≥27 kg/m2 with more than 1 body weight-related coexisting disease). The SMG group (once 2.4 mg, once a week) was treated for 68 weeks, and the average weight loss in the SMG group was 15.3 kg. More patients in the SMG group achieved a weight loss of ≥ 5% (86.4% vs. 31.5%), ≥ 10% (69.1% vs. 12.0%”
From GLP−1 receptor agonists for the treatment of obesity: Role as a promising approach (2023) · cites this paper as [100]
In the citing paper
“In particular, at a dosage of 2.4 mg per week, it has been shown to induce an average weight loss between 9.6% and 17.4%, as well as a reduction in waist circumference and arterial hypertension and an improvement of lipid profile [34,35,36,37,39].”
From GLP-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease: Current Evidence and Future Perspectives (2023) · cites this paper as [34]
In the citing paper
“The STEP trial programme assessed the effect of a high dose of the GLP-1RA semaglutide (2.4 mg once weekly by subcutaneous injection: Weygovy ) and typically noted about a 15% reduction in body weight during treatment periods up to 2 years in overweight and obese adults who did not have T2DM (STEP-1, 3, 4, 5, 8) [16-23].”
From Recent advances in peptide-based therapies for obesity and type 2 diabetes (2024) · cites this paper as [16]
In the citing paper
“The proportion of subjects who lost ≥ 5% of baseline body weight was 86.4–88.7% [15–17, 19].”
From Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review (2022) · cites this paper as [15]
In the citing paper
“Semaglutide resulted in 10.3–17.4% difference in mean weight compared to placebo [15–17, 19].”
From Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review (2022) · cites this paper as [15]
In the citing paper
“Both efficacy benchmark criteria for weight management products were met in STEP 1, 3, 4 and 8 trials [15–17, 19].”
From Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review (2022) · cites this paper as [15]
In the citing paper
“While the STEP 2 trail included 51% female participants [22], the STEP 1, STEP 3 and STEP 4 trials included 73%, 81% and 79% female participants, respectively [15–17]. Thus, STEP 2 has a greater proportion of men (49.1%) than the other trials (19.0–25.9%).”
From Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review (2022) · cites this paper as [15]
In the citing paper
“The percentage of Caucasian participants in each study was 76%, 62%, 76% and 84% for the STEP 1–4 trials, respectively [15–17, 22].”
From Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review (2022) · cites this paper as [15]
In the citing paper
“in the STEP 1 clinical trial, which included 1961 adults with a body mass index above 27 kg/m2, semaglutide 2.4 mg in addition to a lifestyle intervention was associated with a mean change in body weight of −14.9% after 68 weeks [4]”
From What Is Food Noise? A Conceptual Model of Food Cue Reactivity (2023) · cites this paper as [4]
In the citing paper
“the main trials for which data have been published (STEP 1 through STEP 5, STEP 8, and STEP TEENS) did not include participants who reported having symptoms of major depressive disorder within 2 years before screening, which limits their ability to assess psychiatric adverse events in people with a recent history of depression [3,4,93,94,95,96,97].”
From What Is Food Noise? A Conceptual Model of Food Cue Reactivity (2023) · cites this paper as [4]
In the citing paper
“Despite the lack of statistically significant evidence for such association in clinical trials conducted so far [4,92]”
From What Is Food Noise? A Conceptual Model of Food Cue Reactivity (2023) · cites this paper as [4]
In the citing paper
“The trial, which led to the approval of semaglutide for obesity treatment, revealed that up to 40% of total body weight loss could be attributed to lean body mass reduction, exceeding the approximate 25% commonly seen with standard caloric restriction [2].”
From Muscle Loss in Obesity Therapy as a Therapeutic Target: Trial Design and Endpoints for Regulatory Discussions (2025) · cites this paper as [1]
In the citing paper
“According to Johansson, the fundamental contrast lies between dual‐energy X‐ray absorptiometry (DXA) and magnetic resonance imaging (MRI), where recent studies frequently highlight that MRI and CT scans can attribute approximately 50% of adipose tissue volume to what is technically referred to as ‘lean body mass’ [1].”
From Muscle Loss in Obesity Therapy as a Therapeutic Target: Trial Design and Endpoints for Regulatory Discussions (2025) · cites this paper as [1]
In the citing paper
“Trials like STEP 1 and SURMOUNT 1 report changes in lean body mass [1, 9], but often lack details on measurement specificity.”
From Muscle Loss in Obesity Therapy as a Therapeutic Target: Trial Design and Endpoints for Regulatory Discussions (2025) · cites this paper as [1]
In the citing paper
“Compared to agents like semaglutide and tirzepatide (as shown in STEP 1 and SURMOUNT‐1) [1, 9], bimagrumab demonstrates a more favourable ratio of fat‐to‐lean mass loss.”
From Muscle Loss in Obesity Therapy as a Therapeutic Target: Trial Design and Endpoints for Regulatory Discussions (2025) · cites this paper as [1]
In the citing paper
“Compared with other selective GLP-1 analogues, semaglutide is more potent and has higher affinity for GLP-1R, resulting in greater weight loss and glucose-lowering properties (45–47).”
From The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission (2023) · cites this paper as [47]
In the citing paper
“In the STEP‐1 trial, semaglutide 2.4 mg achieved 14.9% weight loss at week 68, with only a modest additional 0.3% (−15.2%) reduction observed at week 104 in STEP‐5, despite nearly doubling treatment duration [29, 33].”
From Efficacy and Safety of Orforglipron in Obese Adults With or Without Diabetes: A Systematic Review and Meta‐Analysis (2025) · cites this paper as [29]
In the citing paper
“Notably, non‐diabetic patients demonstrated greater weight loss (−8.5%) compared to diabetic patients (−4.87%), a finding consistent with previous GLP‐1 agonist studies [29, 30, 31, 32].”
From Efficacy and Safety of Orforglipron in Obese Adults With or Without Diabetes: A Systematic Review and Meta‐Analysis (2025) · cites this paper as [29]
In the citing paper
“These reductions are lower than the effects seen with injectable GLP‐1 receptor agonists such as semaglutide (15%–17% weight loss) and tirzepatide (15%–22% weight loss) but clinically meaningful and comparable to those observed with other oral anti‐obesity agents [14, 29].”
From Efficacy and Safety of Orforglipron in Obese Adults With or Without Diabetes: A Systematic Review and Meta‐Analysis (2025) · cites this paper as [29]
In the citing paper
“Orlistat three-times daily [56][57][58][59] was found in long-term trials to have potential benefits for both weight (mean total loss ≈7%) and cardiovascular risk factors, but placebo-subtracted weight losses are ≈3% and side-effects such oily stools limit its use.60”
From Approach to Obesity Treatment in Primary Care: A Review (2024) · cites this paper as [56]
In the citing paper
“Nausea occurred in 44.2% vs. 17.4%, diarrhea 31.5% vs. 15.9%, vomiting 24.8% vs. 6.6%, and constipation 23.4% vs. 9.5%.”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [13]
In the citing paper
“In the STEP 1 trial, semaglutide recipients experienced GI disorders in 74.2% versus 47.9% with placebo.”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [13]
In the citing paper
“Nausea occurred in 44.2% vs. 17.4%, diarrhea 31.5% vs. 15.9%, vomiting 24.8% vs. 6.6%, and constipation 23.4% vs. 9.5%.”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [13]
In the citing paper
“Discontinuation due to GI events occurred in 4.5% on semaglutide vs. 0.8% on placebo [13].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [13]
In the citing paper
“Nausea occurred in 44.2% vs. 17.4%, diarrhea 31.5% vs. 15.9%, vomiting 24.8% vs. 6.6%, and constipation 23.4% vs. 9.5%.”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [13]
In the citing paper
“Nausea occurred in 44.2% vs. 17.4%, diarrhea 31.5% vs. 15.9%, vomiting 24.8% vs. 6.6%, and constipation 23.4% vs. 9.5%.”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [13]
In the citing paper
“Multiple trials reported the most commonly observed AEs included nausea, diarrhea, constipation, and abdominal discomfort [3,6,9,12,13].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [13]
In the citing paper
“In the STEP 1 trial, semaglutide produced substantial weight loss, of which approximately 30% was attributed to lean tissue, while fat loss predominated [21, 22].”
From Muscle loss and GLP-1R agonists use (2025) · cites this paper as [21]
In the citing paper
“Across all drug classes, the timing of GI AEs strongly implicates the dose-escalation phase as the key driver of intolerance [6,7,13].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [13]
In the citing paper
“Clinical trial evidence consistently shows that GLP-1RA therapy results in significant reductions in fat mass, accompanied by smaller but measurable decreases in lean mass.”
From Muscle loss and GLP-1R agonists use (2025) · cites this paper as [21]
In the citing paper
“GLP-1 receptor agonists (semaglutide, liraglutide, exenatide, orforglipron) consistently produced the highest frequency of GI events among approved pharmacotherapies [6,7,9,10,13].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [13]
In the citing paper
“Gallbladder-related events and rare pancreatitis cases were more frequently observed with GLP-1 based drugs, consistent with their known effects on biliary motility and lipid metabolism rather than direct pancreatic toxicity [4,6,13].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [13]
In the citing paper
“For incretin-based agents, nausea and diarrhea are primarily mediated by delayed gastric emptying, activation of central satiety centers in the hypothalamus, and enhanced vagal signaling that collectively slow motility [4,6,8,11,13].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [13]
In the citing paper
“Individualized titration schedules, reassurance about symptom transience, and short-term symptomatic therapy can maintain adherence and limit discontinuation to below 5–7% once maintenance dosing is achieved [6,11,12,13].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [13]
In the citing paper
“Gallbladder-related events and rare pancreatitis cases were more frequently observed with GLP-1 based drugs, consistent with their known effects on biliary motility and lipid metabolism rather than direct pancreatic toxicity [4,6,13].”
From Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review (2025) · cites this paper as [13]
In the citing paper
“Generally, weight reduction is more rapid during the first 6 months and slows thereafter, with relative plateauing at 18 months [13,15,16].”
In the citing paper
“In the STEP 1 trial, of the average 13.6 kg weight reduction, 8.3 kg (62 %) was fat mass and 5.3 kg (38 %) was lean body mass (including muscle and other non-fat tissues) [14].”
In the citing paper
“During dose escalation in the clinical trials, subjects were allowed to remain at a GLP-1 dose for up to 8 weeks, as needed, to allow GI side effects to dissipate [15,16].”
In the citing paper
“In comparison, the STEP 1 trial that included semaglutide with general nutrition and physical activity instructions demonstrated a 14.9 % weight reduction from baseline (versus 2.4 % with general nutrition and physical activity instructions alone) [14].”
In the citing paper
“the SCALE [13], STEP 1 [14], SURMOUNT [15], and STEP 3 [169] trials each demonstrated substantial weight reduction by combining GLP-1s with regular counseling sessions by RDNs or other qualified healthcare professionals”
In the citing paper
“In STEP 1 and STEP 3, patients on semaglutide lost 14.8–16.0% BW compared to 2.4–5.7% in the placebo group at 68 weeks26,27.”
From Incretin-based therapies for the treatment of obesity-related diseases (2024) · cites this paper as [27]
In the citing paper
“Notably, the STEP-1 clinical trial for semaglutide noted that a significant proportion of weight loss was due to lean mass (∼40 %) [5].”
From Antibody blockade of activin type II receptors preserves skeletal muscle mass and enhances fat loss during GLP-1 receptor agonism (2024) · cites this paper as [5]
In the citing paper
“Nevertheless, using this model we recapitulate lean mass loss as observed in overweight and obese humans treated with GLP-1 receptor agonists.”
From Antibody blockade of activin type II receptors preserves skeletal muscle mass and enhances fat loss during GLP-1 receptor agonism (2024) · cites this paper as [5]
In the citing paper
“The weight loss attributable to lean mass reported here is less than what is reported in humans”
From Antibody blockade of activin type II receptors preserves skeletal muscle mass and enhances fat loss during GLP-1 receptor agonism (2024) · cites this paper as [5]
In the citing paper
“The weight loss observed in a clinical trial of semaglutide is attributable to losses of both fat and lean mass, with ∼40 % of weight loss reported to be fat-free mass [5].”
From Antibody blockade of activin type II receptors preserves skeletal muscle mass and enhances fat loss during GLP-1 receptor agonism (2024) · cites this paper as [5]
In the citing paper
“The magnitude of weight loss observed with GLP1-RA in this real-life patient population is consistent with findings from the SCALE, SUSTAIN, and STEP clinical trials, which are based on patients without bariatric surgery.”
In the citing paper
“The current study includes patients with T2D that have been shown to lose less weight with GLP1-RA therapy [29, 30, 32, 33]”
In the citing paper
“The STEP 1 and 2 studies, investigating the weight effect of semaglutide 2.4 mg weekly versus placebo over 68 weeks, reported a weight loss of 12.4% and 6.2%, respectively [32, 33].”
In the citing paper
“previous studies have shown that GLP1-RAs tend to induce less weight loss in patients with than without T2D [29, 30, 32, 33]”
In the citing paper
“In non-surgical patients with obesity, semaglutide induces clinically important weight loss and improvement in cardiometabolic risk factors [16].”
In the citing paper
“Across the phase 3 STEP program for semaglutide 2.4 mg s.c.weekly plus lifestyle modification in individuals living with obesity without T2D, the body weight reduction from baseline ranged from 12.1% to 18.2%.107-113”
From Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high‐dose GLP‐1 receptor agonists and GLP‐1 receptor‐based co‐agonists (2024) · cites this paper as [112]
In the citing paper
“Additionally, a proportion of people are not able to tolerate the higher doses of GLP-1 RAs due to dose-dependent adverse events making even more difficult for them to achieve the individualized metabolic and WL targets [17,20].”
In the citing paper
“The efficacy of the injectable GLP-1 RAs semaglutide and liraglutide in inducing WL and weight maintenance through appetite reduction has led to clinical trials assessing higher doses of these molecules as treatments for obesity and both semaglutide 2.4 mg once weekly and liraglutide 3 mg once daily have now received approval for chronic weight management [17,18].”
In the citing paper
“The efficacy of the injectable GLP-1 RAs semaglutide and liraglutide in inducing WL and weight maintenance through appetite reduction has led to clinical trials assessing higher doses of these molecules as treatments for obesity and both semaglutide 2.4 mg once weekly and liraglutide 3 mg once daily have now received approval for chronic weight management [17,18].”
In the citing paper
“In addition, a number of oral GLP-1 RAs are under development to offer an alternative option to people reluctant to injectable treatments, with early data for some of them suggesting similar efficacy in glycemia and WL to injectable GLP-1 RAs [17,23].”
In the citing paper
“In addition, a number of oral GLP-1 RAs are under development to offer an alternative option to people reluctant to injectable treatments, with early data for some of them suggesting similar efficacy in glycemia and WL to injectable GLP-1 RAs [17,23].”
In the citing paper
“In the original phase 3 randomized trials for obesity, average weight reduction compared to placebo has ranged from 5.3% to 17.8% after 56 to 72 wk (Table 1), with improvements in several obesity-related risks and complications [[13], [14], [15]].”
In the citing paper
“In the STEP 1 trial, of the average 13.6-kg–weight reduction, 8.3 kg (62%) was fat mass and 5.3 kg (38%) was lean body mass (including muscle and other nonfat tissues) [14].”
In the citing paper
“In comparison, the STEP 1 trial that included semaglutide with general nutrition and physical activity instructions demonstrated a 14.9% weight reduction from baseline (versus 2.4% with general nutrition and physical activity instructions alone) [14].”
In the citing paper
“Although limited direct evidence has evaluated use of GLP-1s with or without RDN-provided MNT, the SCALE [13], STEP 1 [14], SURMOUNT [15], and STEP 3 [178] trials each demonstrated substantial weight reduction by combining GLP-1s with regular counseling sessions by RDNs or other qualified healthcare professionals (such lifestyle support was also provided to the placebo group in each trial).”
In the citing paper
“In STEP 1, individuals randomized to semaglutide achieved an average weight reduction of 14.9% compared to 2.4% for placebo (treatment difference of 12.4%).”
From New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics (2023) · cites this paper as [33]
In the citing paper
“Furthermore, one-third of the semaglutide group lost ≥20% body weight versus only 1.7% achieving this target in the placebo group (33).”
From New Frontiers in Obesity Treatment: GLP-1 and Nascent Nutrient-Stimulated Hormone-Based Therapeutics (2023) · cites this paper as [33]
In the citing paper
“In randomized controlled trials, the long‐acting glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) semaglutide and glucose‐dependent insulinotropic polypeptide (GIP) and GLP‐1 dual receptor agonist tirzepatide have demonstrated greater weight reduction in patients with obesity without T2D compared to other obesity medications (OMs) previously approved by the Food and Drug Administration (FDA) [3,”
From Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status (2025) · cites this paper as [3]
In the citing paper
“The average weight reduction in this cohort was lower than that observed in the main phase 3 trials of semaglutide 2.4 mg (STEP 1) and tirzepatide 5 to 15 mg (SURMOUNT‐1), in which 14.9% and 15.0% and 20.9% weight reduction, respectively, was demonstrated in patients with overweight or obesity (without T2D) plus a lifestyle intervention [3, 4].”
From Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status (2025) · cites this paper as [3]
In the citing paper
“In this study, 20.4% of patients discontinued their obesity pharmacotherapy early, and 32.0% discontinued late, which is considerably higher than the rates of discontinuation at ~1 year in the main phase 3 trials (including 17.1% for semaglutide 2.4 mg injection [STEP 1] and 14.3%–16.4% for tirzepatide 5–15 mg [SURMOUNT‐1] [3, 4]).”
From Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status (2025) · cites this paper as [3]
In the citing paper
“Existing data suggest that marked adipose tissue loss with semaglutide and tirzepatide occurs with concomitant muscle loss202,204,205.”
From Sarcopenic obesity in older adults: a clinical overview (2024) · cites this paper as [204]
In the citing paper
“Nineteen publications reported gallstones or gallbladder-related disorders [11-14,30,36,40,52,62,65,74,77,78,84,85,93,94,103] in 0-3.1%, 0.2-7%, 0-2.9% of patients treated with liraglutide, semaglutide, and tirzepatide, respectively.”
From Symptomatic Adverse Events and Quality of Life Related to Incretin-Based Medicines for Obesity: A Systematic Review Involving >400,000 Subjects (2025) · cites this paper as [13]
In the citing paper
“Changes to lean body mass (LBM) defined as total body weight minus fat mass, and bone mineral density were reported in 8 of the 81 identified publications [12,13,37,45,50,73,75,87].”
From Symptomatic Adverse Events and Quality of Life Related to Incretin-Based Medicines for Obesity: A Systematic Review Involving >400,000 Subjects (2025) · cites this paper as [13]
In the citing paper
“In the STEP 1-4 trials (semaglutide), the proportion of participants experiencing nausea increased from 0 to ~20% from Week 0 to Week 20 (dose escalation or run-in period), then decreased to ~4% by Week 68 (maintenance phase) [13,65,84,93,98].”
From Symptomatic Adverse Events and Quality of Life Related to Incretin-Based Medicines for Obesity: A Systematic Review Involving >400,000 Subjects (2025) · cites this paper as [13]
In the citing paper
“Semaglutide 2.4 mg, for example, has been associated with mean weight loss exceeding 15% of initial body weight over 68 weeks [13]”
From Unintended Consequences of Obesity Pharmacotherapy: A Nutritional Approach to Ensuring Better Patient Outcomes (2025) · cites this paper as [13]
In the citing paper
“In the STEP 1 trial, semaglutide treatment resulted in an average lean mass reduction of 6.9 kg (−13.2%) out of a total 15.3 kg (−14.9%) weight loss, representing approximately 45% of the total weight lost as lean mass [13].”
From Unintended Consequences of Obesity Pharmacotherapy: A Nutritional Approach to Ensuring Better Patient Outcomes (2025) · cites this paper as [13]
In the citing paper
“Several clinical trials of GLP-1 receptor agonists and related pharmacotherapies have reported that a proportion of total weight loss occurs as lean mass, though the magnitude varies by drug, population, and methodology.”
From Unintended Consequences of Obesity Pharmacotherapy: A Nutritional Approach to Ensuring Better Patient Outcomes (2025) · cites this paper as [13]
In the citing paper
“the FDA approved semaglutide in June 2021 for long-term weight management in overweight or people with obesity (31–33).”
From Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system (2022) · cites this paper as [31]
In the citing paper
“Conversely, the first multicenter real-world cohort study reported an average 13.4% loss (97), comparable to the STEP 1 clinical trial data (79), implying a variable response to semaglutide in different trial and real-world settings.”
From GLP-1 and the Neurobiology of Eating Control: Recent Advances (2025) · cites this paper as [79]
In the citing paper
“Gastrointestinal side effects are typically classed as mild or moderate, and reported to subside in most patients following titration up to maintenance doses (77, 79, 104), although they still lead to permanent discontinuation of treatment in 4% to 10% of participants (77, 79, 95).”
From GLP-1 and the Neurobiology of Eating Control: Recent Advances (2025) · cites this paper as [79]
In the citing paper
“Semaglutide represented a step-change in the efficacy of AOMs, achieving previously unseen AOM-mediated weight-loss effects of up to 15% (77‐79), thus approaching the gold standard of bariatric surgery.”
From GLP-1 and the Neurobiology of Eating Control: Recent Advances (2025) · cites this paper as [79]
In the citing paper
“Looking beyond headline weight loss results, substantial response variability exists within patient populations, with the STEP and SURMOUNT trials reporting that 10% to 15% of individuals lose <5% on semaglutide or tirzepatide, respectively, and are thus classed as “nonresponders” (77, 79, 80, 94, 100).”
From GLP-1 and the Neurobiology of Eating Control: Recent Advances (2025) · cites this paper as [79]
In the citing paper
“Furthermore, the 4-year SELECT clinical trial—the longest AOM study of semaglutide to date—reported 8.7% placebo-subtracted weight loss, markedly lower than 12.5% in STEP 1 at 68 weeks (79, 95).”
From GLP-1 and the Neurobiology of Eating Control: Recent Advances (2025) · cites this paper as [79]
In the citing paper
“Notably, GLP-1RA efficacy is lessened in participants with a lower starting weight/BMI or with prior exposure to GLP-1RAs (95, 102), and it is reduced by a third in type 2 diabetics and in male individuals (79, 93, 95‐97, 99).”
From GLP-1 and the Neurobiology of Eating Control: Recent Advances (2025) · cites this paper as [79]
In the citing paper
“The loss of lean body mass is another common side effect of GLP-1RAs, with studies reporting that lean mass loss accounts for ∼45% and ∼25% of total loss for semaglutide (79, 105) and tirzepatide (98), respectively.”
From GLP-1 and the Neurobiology of Eating Control: Recent Advances (2025) · cites this paper as [79]
In the citing paper
“However, the STEP3 trial did include an 8-week low-calorie diet prior to semaglutide initiation (94), which did not result in notably greater weight loss than the STEP1 trial which did not include such a lead-in (79)”
From GLP-1 and the Neurobiology of Eating Control: Recent Advances (2025) · cites this paper as [79]
In the citing paper
“The most successful obesity therapeutics – glucagon-like peptide-1 receptor (GLP1R) agonists – cause aversive responses such as nausea and vomiting1,2, effects which may contribute to their efficacy.”
From Dissociable hindbrain GLP1R circuits for satiety and aversion (2024) · cites this paper as [2]
In the citing paper
“Long-acting GLP-1RAs exert substantial and sustained body weight losses,18”
From The cardioprotective effects of semaglutide exceed those of dietary weight loss in mice with HFpEF (2023) · cites this paper as [18]
In the citing paper
“Long-acting glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated promising weight reduction in recent studies, 14,15 together with improvements in CVD risk factors including waist circumference, systolic blood pressure (SBP), triglycerides, high-density lipoprotein (HDL) cholesterol, and lowdensity lipoprotein (LDL) in individuals with obesity.16,17”
In the citing paper
“In a phase 3 study investigating the effect of semaglutide, a GLP-1 receptor agonist, on weight loss in patients with obesity or overweight, participants who received semaglutide demonstrated improvements in cardiometabolic risk factors.15”
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Metadata
- Authors
- Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., Wharton, S., Yokote, K., Zeuthen, N., & Kushner, R. F.
- Affiliations
- University College London Hospitals NHS Foundation Trust (GB)
- University College Hospital (GB)
- From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy’s and St. Thomas’ NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester — all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University ...
- Northwestern University (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2021-03-18
- Volume
- 384
- Issue
- 11
- Pages
- 989-1002
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W3127371223
- Semantic Scholar
- 00089c657bd5b957b51f67c6c9b80c7d17ce9c5a
- Cited by
- 5,205
- References
- 40
- Citations by year
- 2026: 1566 · 2025: 1350 · 2024: 965 · 2023: 657 · 2022: 386 · 2021: 270
- FWCI
- 332.33
- Type
- journal article
- Language
- en
- Open access
- green
- discovery.ucl.ac.uk
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- HAL (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- obesity, overweight, weight loss, GLP-1 receptor agonists, lifestyle intervention, cardiometabolic risk factors, physical function, nausea and diarrhea, adverse events, weight-related comorbidities, sleep duration, medication adherence, treatment discontinuation, rescue interventions, body mass index
- MeSH terms
- Healthy Lifestyle, Semaglutide, Adult, Body Composition, Cholelithiasis, Diarrhea, Double-Blind Method, Glucagon-Like Peptides, Female, Humans, Injections, Subcutaneous, Lipids, Male, Middle Aged, Nausea, Obesity, Prediabetic State, Weight Loss, Body Mass Index, Anti-Obesity Agents, Glucagon-Like Peptide 1
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