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Cited by 5Pharmacology and Obesity TreatmentDiabetes Treatment and ManagementBariatric Surgery and Outcomes

Symptomatic Adverse Events and Quality of Life Related to Incretin-Based Medicines for Obesity: A Systematic Review Involving >400,000 Subjects

Open access
Kushner, Robert F., Johansen, Odd Erik, Araujo Torres, Krysmaru, Phan, Trà-Mi, Marczewska, Agnieszka·2025·Obesities
DOI 10.3390/obesities5020029
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Abstract

Background/Objectives: Obesity is a chronic, progressive, recurrent disease associated with impaired health, affecting an increasing proportion of the population worldwide. Newer-generation incretin-based therapies (IBTs) (liraglutide, semaglutide, and tirzepatide) have shown greater efficacy than older anti-obesity medications. This systematic literature review provides an overview of the evidence on the symptomatic adverse events (AEs) and patient-reported outcomes of IBTs to facilitate clinical decision-making. Methods: A systematic search was conducted using a predefined search strategy to identify controlled trials and real-world evidence (RWE) studies assessing IBTs. Results: Among 4414 publications identified, 81 (>400,000 participants) were included. Liraglutide (n = 49), semaglutide (n = 34), and tirzepatide (n = 7) were used in 48 clinical and 33 RWE studies. Gastrointestinal (GI) AEs were most common: placebo-subtracted incidences were 5–39% for nausea, −7–39% for diarrhea, 2–31% for constipation, 0–26% for vomiting, and 2–20% for abdominal pain, with no clear difference across IBTs. Most AEs were mild or moderate and mainly occurred during dose escalation. Quality of life outcomes were reported in 27 publications and generally showed improvements with IBTs. Conclusions: This study confirms that GI AEs are common with IBTs. Clinicians should keep the AE profile of IBTs in mind and consider where additional preventative measures may be required.

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic literature review of 81 publications (>400,000 participants) found that gastrointestinal adverse events are the most common side effects of incretin-based therapies (liraglutide, semaglutide, tirzepatide) for obesity, but are mostly mild-to-moderate and concentrated during dose escalation. Quality of life generally improved with treatment, mainly in physical rather than mental domains.

Key findings

  • Among 4414 publications screened, 81 were included (72 unique studies; >400,000 participants), covering liraglutide (49 publications), semaglutide (34), and tirzepatide (7); 47 were RCTs, 33 RWE studies, and 1 non-randomized pilot study.
  • Placebo-subtracted GI AE incidences were 5–39% for nausea, −7–39% for diarrhea, 2–31% for constipation, 0–26% for vomiting, and 2–20% for abdominal pain, with no clear difference across IBTs; most AEs were mild/moderate and occurred during dose escalation.
  • Discontinuation rates due to AEs were low (<3% nausea, ≤2% diarrhea, <1% constipation, <2.1% vomiting, <1.4% abdominal pain), with two RWE outliers (66% and 24.3%).
  • Quality of life was reported in 27 publications (all clinical studies), mostly using IWQoL (n = 16) and SF-36 (n = 16); improvements were generally significant versus placebo, often in physical but not mental domains. Other AEs included hair loss (4.9–7.0% tirzepatide vs 0.9–1.4% placebo), fatigue, and injection site reactions (placebo-adjusted 0–12.5%).

Methods

  • Systematic literature search via Ovid (Embase, MEDLINE, Cochrane Library, EconLit) on 4 June 2024, with predefined free-text and MeSH terms; exclusions included non-weight-related IBT use, type 1 diabetes, and studies with <50 participants.
  • Two independent reviewers screened titles/abstracts then full texts, with a project lead resolving disputes; hand searching added 4 citations.
  • Quality appraisal used Cochrane RoB (RCTs), EPHPP (non-RCTs), and NICE methodology checklists (RWE); data were extracted into pre-designed summary tables with second-reviewer verification.

Limitations

  • Stated by the paper: exclusion of non-approved newer therapies; a 2014-onwards date restriction; exclusion of studies with <50 patients; findings not applicable to T2DM management (obesity dosing ~twice as high); mixed T2DM/non-T2DM populations with no designed comparison; AE differences generally not statistically analyzed; lack of long-term data and no data on patient AE burden.
  • Evident from the text: quality-of-life data came only from clinical studies (no RWE), and the negative effects of GI or nutritional AEs were not captured by the patient-reported outcome tools used, except in one study (Lean et al.).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/obesities5020029

Cites

125 of 126 references verified0 citation errors · 1 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 194 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    Placebo-adjusted discontinuation due to diarrhea was ≤2% in all publications that reported the AE.

    “Placebo-adjusted discontinuation due to diarrhea was ≤2% in all publications that reported the AE [12,36,52,70,94,103].”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [12] Jastreboff, 2022, Tirzepatide once weekly for the treatment of obesity, N. Engl. J. Med. source

      Not checked in the free run.

    • cites [36] Aronne, 2024, Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: The SURMOUNT-4 randomized clinical trial, JAMA source

      Not checked in the free run.

    • cites [52] Garvey, 2023, Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): A double-blind, randomised, multicentre, placebo-controlled, phase 3 trial, Lancet source

      Not checked in the free run.

    • cites [70] Ma, 2024, Efficacy and safety of tirzepatide in people with type 2 diabetes by baseline body mass index: An exploratory subgroup analysis of SURPASS-AP-Combo, Diabetes Obes. Metab. source

      Not checked in the free run.

    • cites [94] Wadden, 2023, Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: The SURMOUNT-3 phase 3 trial, Nat. Med. source

      Not checked in the free run.

    • cites [103] Zhao, 2024, Tirzepatide for Weight Reduction in Chinese Adults with Obesity: The SURMOUNT-CN Randomized Clinical Trial, JAMA source

      Not checked in the free run.

  • Findingown data

    The distribution of values of RWE data for nausea showed no clear difference across individual IBTs.

    “The distribution of values of RWE data showed no clear difference across individual IBTs.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In the 60 publications that captured nausea, severity was generally mild or moderate.

    “In the 60 publications that captured nausea (including 7 reporting nausea and vomiting as a combined AE) (Table S6), severity was generally mild or moderate.”
    Quote in the paperNot a substantial claim
  • Findingcitation

    In STEP 8, severe GI AEs were reported in 2.4% of patients treated with liraglutide and 3.2% of patients treated with semaglutide.

    “In STEP 8 [85], severe GI AEs were reported in 2.4% and 3.2% of patients treated with liraglutide and semaglutide, respectively.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [85] Rubino, 2022, Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults with Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial, JAMA source

      Not checked in the free run.

  • Findingown data

    In total, more than 400,000 participants were involved across the studies.

    “In total, more than 400,000 participants were involved across the studies.”
    Quote in the paperSubstantial claim
  • May combine two claims. 68
  • Classified as probably not a substantial claim. 44

  • May combine two claims.

    Findingown data

    The placebo-adjusted incidence ranges for constipation were 1.8-31% for liraglutide, 5.3-23% for semaglutide, and 4.4-16.2% for tirzepatide.

    “the incidence ranges for liraglutide, semaglutide, and tirzepatide were 1.8-31%, 5.3-23%, and 4.4-16.2%,respectively.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The placebo-adjusted incidence ranges of clinical data for nausea were 11-43.3% for liraglutide, 9.1-38.7% for semaglutide, and 5.4-30.8% for tirzepatide.

    “The placebo-adjusted incidence ranges of clinical data for liraglutide, semaglutide, and tirzepatide were 11-43.3%,9.1-38.7%,and 5.4-30.8%,respectively.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    1391 duplicates were excluded.

    “The electronic database searches yielded 4414 publications (Figure 1), with 1391 duplicates subsequently excluded.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    One publication measured serious nausea AEs; however, no AEs were reported in the study.

    “One publication measured serious nausea AEs; however, no AEs were reported in the study [68].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Lean, 2014, Tolerability of nausea and vomiting and associations with weight loss in a randomized trial of liraglutide in obese, non-diabetic adults, Int. J. Obes. source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The incidence ranges of RWE data for constipation were 1.2-25.6% for liraglutide, 2.6-23% for semaglutide, and 3% (n = 1) for tirzepatide.

    “The incidence ranges of RWE data were 1.2-25.6%,2.6-23%, and 3% (n = 1) for liraglutide, semaglutide, and tirzepatide, respectively.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In the STEP 1-3 pooled analysis, 4.1% of patients on semaglutide reported severe GI AEs and 1.3% reported serious GI AEs, compared with 0.9% and 0.4% for the placebo group, respectively.

    “In the STEP 1-3 pooled analysis, 4.1% and 1.3% of patients on semaglutide reported severe and serious GI AEs, respectively, compared with 0.9% and 0.4% for the placebo group, respectively [98].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [98] Wharton, 2022, Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss, Diabetes Obes. Metab. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    The 81 included publications related to 72 unique studies.

    “Hand searching identified four additional citations that met eligibility criteria, resulting in 81 included publications [11][12][13][14]21, relating to 72 unique studies (Supplementary Materials Table S6).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The electronic database searches yielded 4414 publications.

    “The electronic database searches yielded 4414 publications (Figure 1), with 1391 duplicates subsequently excluded.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Incidence ranges of RWE data for nausea were 4-33.9% for liraglutide, 9.4-38% for semaglutide, and 15% (n = 1) for tirzepatide.

    “Incidence ranges of RWE data were 4-33.9%,9.4-38% and 15% (n = 1) for liraglutide, semaglutide, and tirzepatide, respectively.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The incidence ranges of RWE data for diarrhea were 0.7-10% for liraglutide and 2-10.5% for semaglutide, with no clear difference between semaglutide and liraglutide.

    “The incidence ranges of RWE data for liraglutide and semaglutide were 0.7-10%, and 2-10.5%,respectively, with no clear difference between semaglutide and liraglutide (Figure 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    In STEP 4, 2.1% of patients reported severe GI AEs and 0.2% reported serious GI AEs on semaglutide, compared with 1.9% and 1.5% of patients that switched to placebo, respectively.

    “In STEP 4, 2.1% and 0.2% of patients reported severe and serious GI AEs on semaglutide, respectively, compared with 1.9% and 1.5% of patients that switched to placebo, respectively [98].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [98] Wharton, 2022, Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss, Diabetes Obes. Metab. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Among the included publications, 47 were randomized control trials, 33 were real-world evidence studies, and 1 was a nonrandomized pilot study.

    “Among these, 47 publications were randomized control trials (RCTs), 33 were real-world evidence (RWE) studies, and 1 study was a nonrandomized pilot study [37].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] Capristo, 2018, Intensive lifestyle modifications with or without liraglutide 3mg vs. sleeve gastrectomy: A three-arm non-randomised, controlled, pilot study, Diabetes Metab. source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The identified publications evaluated liraglutide (49 publications), semaglutide (34 publications), and tirzepatide (7 publications).

    “The identified publications evaluated liraglutide (49 publications), semaglutide (34 publications), and tirzepatide (7 publications).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Constipation was reported in 55 publications, and occurred at higher rates with IBTs than placebos, but never as a severe or serious AE.

    “Constipation was reported in 55 publications, and occurred at higher rates with IBTs than placebos, but never as a severe or serious AE (Table S6).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The placebo-adjusted incidence ranges for diarrhea were -7.3-20.1% for liraglutide, 1.9-33% for semaglutide, and 5.9-38.8% for tirzepatide.

    “The placebo-adjusted incidence ranges for liraglutide, semaglutide, and tirzepatide were -7.3-20.1%,1.9-33%, and 5.9-38.8%,respectively.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Hand searching identified four additional citations that met eligibility criteria, resulting in 81 included publications.

    “Hand searching identified four additional citations that met eligibility criteria, resulting in 81 included publications [11][12][13][14]21, relating to 72 unique studies (Supplementary Materials Table S6).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Diarrhea occurred at higher incidence with IBTs than placebo and was typically mild or moderate, transient, and occurred during the dose-escalation phase.

    “Diarrhea (56 publications) occurred at higher incidence with IBTs than placebo and was typically mild or moderate (where severity was reported) [12,36,52,70,94,103], transient, and occurred during the dose-escalation phase (where timing was reported) [12,94,103] (Table S6).”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [12] Jastreboff, 2022, Tirzepatide once weekly for the treatment of obesity, N. Engl. J. Med. source

      Not checked in the free run.

    • cites [36] Aronne, 2024, Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: The SURMOUNT-4 randomized clinical trial, JAMA source

      Not checked in the free run.

    • cites [52] Garvey, 2023, Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): A double-blind, randomised, multicentre, placebo-controlled, phase 3 trial, Lancet source

      Not checked in the free run.

    • cites [70] Ma, 2024, Efficacy and safety of tirzepatide in people with type 2 diabetes by baseline body mass index: An exploratory subgroup analysis of SURPASS-AP-Combo, Diabetes Obes. Metab. source

      Not checked in the free run.

    • cites [94] Wadden, 2023, Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: The SURMOUNT-3 phase 3 trial, Nat. Med. source

      Not checked in the free run.

    • cites [103] Zhao, 2024, Tirzepatide for Weight Reduction in Chinese Adults with Obesity: The SURMOUNT-CN Randomized Clinical Trial, JAMA source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The placebo-adjusted incidence of nausea with IBTs in clinical studies overall indicated an increased rate versus placebo and appeared to be generally higher for liraglutide and semaglutide than tirzepatide.

    “The placebo-adjusted incidence (subtracting the percentage of patients with an AE in placebo/comparator arm from the intervention arm) of nausea with IBTs in clinical studies overall indicated an increased rate (vs placebo) and appeared to be generally higher for liraglutide and semaglutide than tirzepatide (Figure 2).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Screening based on title and abstract excluded 2429 out of 3023 citations, resulting in 594 citations to be screened based on full publications.

    “Screening based on title and abstract led to the exclusion of 2429 out of the remaining 3023 citations, resulting in 594 citations to be screened based on the full publications.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Full-text screening resulted in the inclusion of 77 publications in the systematic literature review.

    “Full-text screening resulted in the inclusion of 77 publications in the systematic literature review (SLR).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The placebo-adjusted incidences for abdominal pain were 1.5-20% for liraglutide, 2-16.6% for semaglutide, and 1.6-14.3% for tirzepatide.

    “The placebo-adjusted incidences for liraglutide, semaglutide, and tirzepatide were 1.5-20%, 2-16.6%, and 1.6-14.3%,respectively.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    One publication reported a single AE of severe stomach pain.

    “One publication reported a single AE of severe stomach pain [83].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [83] Richards, 2023, A remotely delivered, semaglutide-supported specialist weight management program: Preliminary findings from a retrospective service evaluation, JMIR Form. Res. source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The incidence ranges of RWE data for vomiting were 0-15.3% for liraglutide, 1-38% for semaglutide, and 15% (n = 1) for tirzepatide.

    “The incidence ranges of RWE data for liraglutide, semaglutide, and tirzepatide were 0-15.3%, 1-38%, and 15% (n = 1), respectively.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Among publications with an IBT vs. placebo comparison, five and four reported numerically lower and higher AE incidences in the placebo cohorts, respectively, suggesting no consistent trend.

    “Among publications with an IBT vs. placebo comparison, five and four reported numerically lower and higher AE incidences in the placebo cohorts, respectively, suggesting no consistent trend.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The placebo-adjusted incidence ranges for vomiting were 0-21% for liraglutide, 7-25.7% for semaglutide, and 4.5-15.4% for tirzepatide.

    “The placebo-adjusted incidence ranges for liraglutide, semaglutide, and tirzepatide were 0-21%, 7-25.7%, and 4.5-15.4%,respectively.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Incidence ranges for RWE data for abdominal pain were 0-8.3% for liraglutide, 0.9-11.5% for semaglutide, and 3% (n = 1) for tirzepatide.

    “Incidence ranges for RWE data for liraglutide, semaglutide, and tirzepatide were 0-8.3%, 0.9-11.5%,and 3% (n = 1), respectively.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The net difference between treatment and placebo arms for pancreatitis was 0% in 11 publications and <1% in the remaining six.

    “The net difference between treatment and placebo arms was 0% in 11 publications and <1% in the remaining six.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Nineteen publications reported gallstones or gallbladder-related disorders in 0-3.1% of patients treated with liraglutide, 0.2-7% with semaglutide, and 0-2.9% with tirzepatide.

    “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.”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [11] Garvey, 2022, Two-year effects of semaglutide in adults with overweight or obesity: The STEP 5 trial, Nat. Med. source

      Not checked in the free run.

    • cites [12] Jastreboff, 2022, Tirzepatide once weekly for the treatment of obesity, N. Engl. J. Med. source

      Not checked in the free run.

    • cites [13] Wilding, 2021, Once-weekly semaglutide in adults with overweight or obesity, N. Engl. J. Med. source

      Not checked in the free run.

    • cites [14] Lincoff, 2023, Semaglutide and cardiovascular outcomes in obesity without diabetes, N. Engl. J. Med. source

      Not checked in the free run.

    • cites [30] Alabduljabbar, 2024, Weight loss response in patients with obesity treated with injectable semaglutide in a real-world setting, Endocrine source

      Not checked in the free run.

    • cites [36] Aronne, 2024, Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: The SURMOUNT-4 randomized clinical trial, JAMA source

      Not checked in the free run.

    • cites [40] Davies, 2021, Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): A randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial, Lancet source

      Not checked in the free run.

    • cites [52] Garvey, 2023, Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): A double-blind, randomised, multicentre, placebo-controlled, phase 3 trial, Lancet source

      Not checked in the free run.

    • cites [62] Kadowaki, 2022, Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): A randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial, Lancet Diabetes Endocrinol. source

      Not checked in the free run.

    • cites [65] Kyrillos, 2022, Semaglutide 2.4-mg injection as a novel approach for chronic weight management, Am. J. Manag. Care source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Reporting of body composition outcomes was heterogeneous (vs placebo/comparator or vs baseline, kg vs percentage change).

    “Reporting of outcomes was heterogeneous (vs placebo/comparator or vs. baseline, kg vs. percentage change), and are summarized in Table 1.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Fifty-four publications reported vomiting, with only one vomiting event reported as an SAE.

    “Fifty-four publications reported vomiting (seven publications reported nausea and vomiting as a combined AE) (Table S6), with only one vomiting event reported as an SAE [68].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Lean, 2014, Tolerability of nausea and vomiting and associations with weight loss in a randomized trial of liraglutide in obese, non-diabetic adults, Int. J. Obes. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    One publication reported changes in bone mineral density.

    “One publication reported changes in bone mineral density [73].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [73] Mok, 2023, Safety and Efficacy of Liraglutide, 3.0 mg, Once Daily vs Placebo in Patients with Poor Weight Loss Following Metabolic Surgery: The BARI-OPTIMISE Randomized Clinical Trial, JAMA Surg. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In one semaglutide RWE study, the discontinuation rate was 24.6%; however, the population was small (n = 61).

    “In one semaglutide RWE study, the discontinuation rate was 24.6%; however, the population was small (n = 61) [39].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Cornet, 2023, Mo1918: Gastrointestinal Symptoms from Semaglutide Are Common in Real-World Clinical Practice, Though Medication Discontinuation Rates Are Similar among Patients with or without Prior Digestive Complaints, Gastroenterology source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Discontinuations due to abdominal pain were reported in three publications and ranged from 0 to 1.4% (placebo-adjusted).

    “Discontinuations due to abdominal pain were reported in three publications [12,36,104] and ranged from 0 to 1.4% (placebo-adjusted).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [12] Jastreboff, 2022, Tirzepatide once weekly for the treatment of obesity, N. Engl. J. Med. source

      Not checked in the free run.

    • cites [36] Aronne, 2024, Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: The SURMOUNT-4 randomized clinical trial, JAMA source

      Not checked in the free run.

    • cites [104] Zhou, 2022, Difference in Gastrointestinal Risk Associated with Use of GLP-1 Receptor Agonists: A Real-World Pharmacovigilance Study, Diabetes Metab. Syndr. Obes. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Placebo-adjusted discontinuation due to vomiting AEs was reported by five publications and ranged from 0 to 2.1%.

    “Placebo-adjusted discontinuation due to vomiting AEs was reported by five publications [12,36,52,94,103] and ranged from 0 to 2.1%.”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [12] Jastreboff, 2022, Tirzepatide once weekly for the treatment of obesity, N. Engl. J. Med. source

      Not checked in the free run.

    • cites [36] Aronne, 2024, Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: The SURMOUNT-4 randomized clinical trial, JAMA source

      Not checked in the free run.

    • cites [52] Garvey, 2023, Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): A double-blind, randomised, multicentre, placebo-controlled, phase 3 trial, Lancet source

      Not checked in the free run.

    • cites [94] Wadden, 2023, Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: The SURMOUNT-3 phase 3 trial, Nat. Med. source

      Not checked in the free run.

    • cites [103] Zhao, 2024, Tirzepatide for Weight Reduction in Chinese Adults with Obesity: The SURMOUNT-CN Randomized Clinical Trial, JAMA source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Severe or serious acute gallbladder disease was reported in two patients (0.7%) with tirzepatide (zero in the placebo group) by Wadden et al. 2023, and seven patients (0.9%) with tirzepatide (three [0.9%] in the placebo group) by Aronne et al. 2024.

    “Severe or serious acute gallbladder disease was reported in two patients (0.7%) with tirzepatide (zero in the placebo group) by Wadden et al. 2023 [94], and seven patients (0.9%) with tirzepatide (three [0.9%] in the placebo group) by Aronne et al. 2024 [36].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [94] Wadden, 2023, Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: The SURMOUNT-3 phase 3 trial, Nat. Med. source

      Not checked in the free run.

    • cites [36] Aronne, 2024, Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: The SURMOUNT-4 randomized clinical trial, JAMA source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Twenty-seven publications (all clinical studies) reported quality of life outcomes.

    “Twenty-seven publications (all clinical studies) reported quality of life outcomes [8,[12][13][14]36,42,51,52,58,[61][62][63][64][65][66][67][68]71,73,74,77,81,84,93,94,96,103].”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The placebo-adjusted incidence of any SAE ranged from -13.7-3.2% for liraglutide, -3.9-7.2% for semaglutide, and -3.9-2.6% for tirzepatide.

    “The placeboadjusted incidence of any SAE ranged from -13.7-3.2%,-3.9-7.2%, and -3.9-2.6% for liraglutide, semaglutide, and tirzepatide, respectively (where negative values indicate a higher incidence of SAEs in the placebo/control arm).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The IWQoL questionnaire (n=16) and SF-36 (n=16) were the most frequently used quality-of-life instruments among the included studies.

    “The Impact of Weight on Quality of Life (IWQoL) questionnaire (n = 16) [8,13,36,42,51,52,[62][63][64][65]67,68,73,74,81,94,103], and the Short-Form 36 (SF-36) (n = 16) [8,12,13,36,51,[61][62][63]65,67,74,81,84,93,94,96,103] were most frequently used.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Dermatological AEs were reported in 29 publications, of which 24 reported injection site reactions with a placebo-adjusted incidence range of 0-12.5%.

    “Dermatological AEs were reported in 29 publications [11][12][13]30,40,43,45,49,58,60,62,66,67,71,[73][74][75]78,81,83,85,87,88,[92][93][94]96,102], of which 24 reported injection site reactions (including bruising, euthymia, irritation, hematoma and itching) with a placebo-adjusted incidence range of 0-12.5%.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11][12][13]30,40,43,45,49,58,60,62,66,67,71,[73][74][75]78,81,83,85,87,88,[92][93][94]96,102]

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    In the SCALE clinical studies (liraglutide), most AEs were mild or moderate in severity, and occurred primarily within the first four to eight weeks of treatment (during dose escalation).

    “In the SCALE clinical studies (liraglutide), most AEs were mild or moderate in severity, and occurred primarily within the first four to eight weeks of treatment (during dose escalation).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [42] Davies, 2015, Efficacy of Liraglutide for Weight Loss Among Patients with Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial, JAMA source

      Not checked in the free run.

    • cites [67] Astrup, 2017, 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: A randomised, double-blind trial, Lancet source

      Not checked in the free run.

    • cites [81] Astrup, 2015, A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management, N. Engl. J. Med. source

      Not checked in the free run.

    • cites [95] Wadden, 2020, Liraglutide 3.0 mg and Intensive Behavioral Therapy (IBT) for Obesity in Primary Care: The SCALE IBT Randomized Controlled Trial, Obesity source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Seven publications evaluated semaglutide: four clinical and three RWE studies.

    “Seven publications evaluated semaglutide: four clinical and three RWE studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In the SURMOUNT clinical trials (tirzepatide), AEs were also most frequent during the dose-escalation phase (first 20 weeks), with the proportion of patients experiencing AEs decreasing up to the trial endpoint.

    “In the SURMOUNT clinical trials (tirzepatide), AEs were also most frequent during the dose-escalation phase (first 20 weeks), with the proportion of patients experiencing AEs decreasing up to the trial endpoint [12,36,52,94,103].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [12] Jastreboff, 2022, Tirzepatide once weekly for the treatment of obesity, N. Engl. J. Med. source

      Not checked in the free run.

    • cites [36] Aronne, 2024, Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: The SURMOUNT-4 randomized clinical trial, JAMA source

      Not checked in the free run.

    • cites [52] Garvey, 2023, Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): A double-blind, randomised, multicentre, placebo-controlled, phase 3 trial, Lancet source

      Not checked in the free run.

    • cites [94] Wadden, 2023, Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: The SURMOUNT-3 phase 3 trial, Nat. Med. source

      Not checked in the free run.

    • cites [103] Zhao, 2024, Tirzepatide for Weight Reduction in Chinese Adults with Obesity: The SURMOUNT-CN Randomized Clinical Trial, JAMA source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Immune system disorders were investigated in one publication, but there were no events reported.

    “Immune system disorders were investigated in one publication, but there were no events reported [102].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [102] Xiong, 2024, Adverse Events of Oral GLP-1 Receptor Agonist (Semaglutide Tablets): A Real-World Study Based on FAERS from 2019 to 2023, Diabetes Ther. source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Overall placebo-subtracted incidences across IBTs were 5-39% for nausea, -7-39% for diarrhea, 2-31% for constipation, 0-26% for vomiting, and 2-20% for abdominal pain.

    “Gastrointestinal (GI) AEs were most common: placebo-subtracted incidences were 5-39% for nausea, -7-39% for diarrhea, 2-31% for constipation, 0-26% for vomiting, and 2-20% for abdominal pain, with no clear difference across IBTs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    Liraglutide was evaluated in 11 publications, of which 8 were clinical studies and 3 were RWE studies.

    “Liraglutide was evaluated in 11 publications, of which 8 were clinical studies and 3 were RWE studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In almost all included studies, IBT groups showed significant improvement in functional measures compared with placebo groups, although this was often observed for physical function but not mental domain scores.

    “In almost all of these studies, a significant improvement in functional measures was observed for the IBT groups compared with the placebo groups, although this was often observed for physical function, but not mental domain scores.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Quality of life outcomes were reported in 27 publications and generally showed improvements with IBTs.

    “Quality of life outcomes were reported in 27 publications and generally showed improvements with IBTs.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Most AEs were mild or moderate and mainly occurred during dose escalation.

    “Most AEs were mild or moderate and mainly occurred during dose escalation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Other dermatological AEs reported were rash (3.6%), pruritus (1.7%), urticaria (3%), cellulitis (0-<1%), and oedema peripheral (6.5%).

    “Other dermatological AEs reported were rash (3.6%) [78], pruritus (1.7%) [43], urticaria (3%) [73], cellulitis (0-<1%) [67,81,93], and oedema peripheral (6.5%) [67].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [78] Park, 2021, Effectiveness of liraglutide 3 mg for the treatment of obesity in a real-world setting without intensive lifestyle intervention, Int. J. Obes. source

      Not checked in the free run.

    • cites [43] Dobbie, 2024, Liraglutide 3.0 mg in the treatment of adults with obesity and prediabetes using real-world UK data: A clinical evaluation of a multi-ethnic population, Clin. Obes. source

      Not checked in the free run.

    • cites [73], [67,81,93], [67]

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    SAEs occurring in >5% of patients were reported in 26 studies, with 9 publications reporting SAEs in >10% of patients.

    “SAEs occurring in >5% of patients were reported in 26 studies [11][12][13][14]35,40,42,51,52,58,62,63,[65][66][67]70,74,77,[84][85][86]93,94,96,103,104], with 9 publications reporting SAEs in >10% of patients [11,14,66,67,85,86,89,103,104].”
    Quote in the paperNot a substantial claim0 of 10 sources checked
    • cites [11][12][13][14]35,40,42,51,52,58,62,63,[65][66][67]70,74,77,[84][85][86]93,94,96,103,104]

      Not checked in the free run.

    • cites [11] Garvey, 2022, Two-year effects of semaglutide in adults with overweight or obesity: The STEP 5 trial, Nat. Med. source

      Not checked in the free run.

    • cites [14] Lincoff, 2023, Semaglutide and cardiovascular outcomes in obesity without diabetes, N. Engl. J. Med. source

      Not checked in the free run.

    • cites [66] Larsen, 2017, Effect of Liraglutide Treatment on Prediabetes and Overweight or Obesity in Clozapine- or Olanzapine-Treated Patients with Schizophrenia Spectrum Disorder: A Randomized Clinical Trial, JAMA Psychiatry source

      Not checked in the free run.

    • cites [67] Astrup, 2017, 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: A randomised, double-blind trial, Lancet source

      Not checked in the free run.

    • cites [85] Rubino, 2022, Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults with Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial, JAMA source

      Not checked in the free run.

    • cites [86] Ryan, 2024, Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial, Nat. Med. source

      Not checked in the free run.

    • cites [89] Shu, Y., He, X., Wu, P., Liu, Y., Ding, Y., and Zhang, Q. (2022). Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system. Front. Public Health, 10. source

      Not checked in the free run.

    • cites [103] Zhao, 2024, Tirzepatide for Weight Reduction in Chinese Adults with Obesity: The SURMOUNT-CN Randomized Clinical Trial, JAMA source

      Not checked in the free run.

    • cites [104] Zhou, 2022, Difference in Gastrointestinal Risk Associated with Use of GLP-1 Receptor Agonists: A Real-World Pharmacovigilance Study, Diabetes Metab. Syndr. Obes. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Two studies compared IBTs with lifestyle modification programs and one compared liraglutide and lifestyle modification with sleeve gastrectomy.

    “while two studies compared IBTs with lifestyle modification programs [61,90] and one compared liraglutide and lifestyle modification with sleeve gastrectomy [37]”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [61] Jensen, 2024, 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, eClinicalMedicine source

      Not checked in the free run.

    • cites [90] Silver, 2023, Effect of the glucagon-like peptide-1 receptor agonist liraglutide, compared to caloric restriction, on appetite, dietary intake, body fat distribution and cardiometabolic biomarkers: A randomized trial in adults with obesity and prediabetes, Diabetes Obes. Metab. source

      Not checked in the free run.

    • cites [37] Capristo, 2018, Intensive lifestyle modifications with or without liraglutide 3mg vs. sleeve gastrectomy: A three-arm non-randomised, controlled, pilot study, Diabetes Metab. source

      Not checked in the free run.

  • May combine two claims.

    Findingreasoning

    For all outcomes, observed incidence ranges of AEs were wide, due to variation in trial design, population, setting, and intrinsic experimental variability.

    “For all outcomes, the observed incidence ranges of AEs were wide, due to the variation in trial design, population, and setting, as well as intrinsic experimental variability.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Only one publication from this SLR recorded calorie intake, and none recorded dietary composition.

    “only one publication from this SLR recorded calorie intake [37], and none recorded dietary composition.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Capristo, 2018, Intensive lifestyle modifications with or without liraglutide 3mg vs. sleeve gastrectomy: A three-arm non-randomised, controlled, pilot study, Diabetes Metab. source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Gallbladder disorders were rare and only reported in a small number of studies.

    “Gallbladder disorders, listed under”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [107] FDA (2025, January 10). Ozempic, FDA Label, Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/209637s032lbl.pdf.

      Not checked in the free run.

    • cites [108] FDA (2025, January 10). Mounjaro, FDA Label, Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/215866s010s015s022lbl.pdf.

      Not checked in the free run.

    • cites [109] FDA (2025, January 10). Saxenda, FDA Label, Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/206321s019lbl.pdf.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    Dermatological AEs were not systematically listed in all publications.

    “Dermatological AEs were not systematically listed in all publications”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    The findings of the 2024 meta-analysis were largely aligned with ours.

    “Their findings were largely aligned with ours.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Abdominal pain was less common, reported by 0-10% of patients after adjustment for placebo.

    “Abdominal pain was less common, reported by 0-10% of patients (after adjustment for placebo).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    More women than men were included in the studies identified.

    “More women than men were included in the studies identified in the publications.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    In the graphs presented, the difference in AE incidence between RWE and clinical trials is masked by placebo adjustment, making incidence appear similar.

    “In the graphs presented, this fact is masked by the placebo adjustment, which makes the incidence appear similar.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Rates of discontinuation due to AEs were low (<3% for nausea, ≤2% for diarrhea, <1% for constipation, <2.1% for vomiting, and <1.4% for abdominal pain), with the exception of two RWE studies (66% and 24.3%), which should be considered outliers.

    “Rates of discontinuation due to AEs were low (<3% for nausea, ≤2% for diarrhea, <1% for constipation, <2.1% for vomiting, and <1.4% for abdominal pain), with the exception of two RWE studies (66% and 24.3%, respectively), which should be considered as outliers [39,69].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [39] Cornet, 2023, Mo1918: Gastrointestinal Symptoms from Semaglutide Are Common in Real-World Clinical Practice, Though Medication Discontinuation Rates Are Similar among Patients with or without Prior Digestive Complaints, Gastroenterology source

      Not checked in the free run.

    • cites [69] Lee, 2023, Weight loss and side-effects of liraglutide and lixisenatide in obesity and type 2 diabetes mellitus, Prim. Care Diabetes source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    Non-GI-related AEs included hair loss and fatigue, both reported in several publications.

    “Non-GI-related AEs included hair loss and fatigue, both reported in several publications.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Currently, there is a lack of data on dietary intakes of patients taking IBTs and on outcomes in terms of macro- and micronutrient deficiencies.

    “Currently, there is a lack of data on dietary intakes of patients taking IBTs and on outcomes in terms macro-and micronutrient deficiencies”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    There was a lack of long-term data and no data reporting the burden of AEs on patients have been identified.

    “There was also a lack of long-term data and no data reporting the burden of AEs on patients have been identified.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Findingnone given

    Their findings generally align with those reported here.

    “Their findings generally align with those reported here.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    IBTs offer great efficacy and improvements in HRQoL.

    “IBTs offer great efficacy and improvements in HRQoL”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    A systematic search was conducted via the Ovid platform on 4 June 2024 using a predefined search strategy in the Embase, MEDLINE, Cochrane Library, and EconLit electronic databases.

    “A systematic search was conducted via the Ovid platform (Wolters Kluwer, Alphen aan den Rijn, The Netherlands) on 4 June 2024 using a predefined search strategy in the Embase (1980-present), MEDLINE (1946-present), the Cochrane Library, and EconLit (1961-present) electronic databases.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Studies where IBTs were used for non-weight-related conditions, studies in type 1 diabetes mellitus, and those with <50 participants were excluded.

    “We excluded studies where IBTs were used for non-weight-related conditions, studies in type 1 diabetes mellitus, and those with <50 participants (see Table S1 for full eligibility criteria).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Reporting of attrition and detection bias was unclear in 23/41 and 18/41 publications, respectively.

    “Based on the Cochrane RoB tool, the quality of the RCT studies was rated as high, although there was one open-label study, and reporting of attrition and detection bias was unclear in 23/41 and 18/41 publications, respectively.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    For the RWE publications, the assessment was generally positive, or the questions were not applicable.

    “For the RWE publications, the assessment was generally positive, or the questions were not applicable.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] National Institute for Health and Care Excellence (NICE) (2025, April 08). The Guidelines Manual: Appendices B-I. Available online: https://www.nice.org.uk/process/pmg6/resources/the-guidelines-manual-appendices-bi-2549703709/chapter/appendix-d-methodology-checklist-cohort-studies.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    There was one open-label study among the RCTs.

    “Based on the Cochrane RoB tool, the quality of the RCT studies was rated as high, although there was one open-label study, and reporting of attrition and detection bias was unclear in 23/41 and 18/41 publications, respectively.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Two independent reviewers evaluated all identified citations based on title/abstract and full publications for inclusion or exclusion.

    “Two independent reviewers evaluated all identified citations based on title/abstract (first pass).Subsequently, two independent reviewers examined full publications of relevant citations (second pass) for inclusion or exclusion.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    A second reviewer conducted quality assessments of the extracted data.

    “A second reviewer conducted quality assessments of the extracted data.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductcitation

    Quality appraisal of randomized trials, non-RCTs, and RWE was conducted using the Cochrane risk-of-bias tool, the EPHPP Quality Assessment Tool, and the NICE guidelines manual methodology checklist, respectively.

    “Quality appraisal of randomized trials, non-RCTs, and RWE was conducted using the Cochrane risk-of-bias (RoB) tool [26], the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies [27], and the methodology checklist provided in Appendix D of the NICE guidelines manual [28], respectively.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [26] Higgins, 2011, The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials, BMJ source

      Not checked in the free run.

    • cites [27] Effective Public Health Practice Project (EPHPP) (2025, April 08). Quality Assessment Tool for Quantitative Studies. Available online: https://www.ephpp.ca/quality-assessment-tool-for-quantitative-studies/.

      Not checked in the free run.

    • cites [28] National Institute for Health and Care Excellence (NICE) (2025, April 08). The Guidelines Manual: Appendices B-I. Available online: https://www.nice.org.uk/process/pmg6/resources/the-guidelines-manual-appendices-bi-2549703709/chapter/appendix-d-methodology-checklist-cohort-studies.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A modeling study by Moll et al., 2024, used data from eight RCTs to calculate the risks of individual AEs associated with treatment with liraglutide, semaglutide, or tirzepatide.

    “A modeling study by Moll et al., 2024 [123], used data from eight RCTs to calculate the risks of individual AEs associated with treatment with liraglutide, semaglutide, or tirzepatide.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [123] Moll, 2024, GLP-1 receptor agonists for weight reduction in people living with obesity but without diabetes: A living benefit–harm modelling study, eClinicalMedicine source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Historically, pancreatitis has been a concern for IBTs.

    “Historically, pancreatitis has been a concern for IBTs [91,105].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [91] Sodhi, 2023, Risk of Gastrointestinal Adverse Events Associated with Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss, JAMA source

      Not checked in the free run.

    • cites [105] Singh, 2013, Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: A population-based matched case-control study, JAMA Intern. Med. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The calculated risks were generally higher for tirzepatide than the other IBTs based on the limited sample included.

    “The calculated risks were generally higher for tirzepatide than the other IBTs based on the limited sample included.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [123] Moll, 2024, GLP-1 receptor agonists for weight reduction in people living with obesity but without diabetes: A living benefit–harm modelling study, eClinicalMedicine source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    The lack of systematic listing of dermatological AEs is most likely due to heterogeneity in study observations and method of data capture.

    “most likely due to heterogeneity in study observations and the method of data capture.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Premisecitation

    The body of evidence around the safety of IBTs for the treatment of obesity continues to grow.

    “The body of evidence around the safety of IBTs for the treatment of obesity continues to grow”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [122] Bhattacharyya, 2024, Mortality and Serious Adverse Events Associated with Glucagon-Like Peptide-1 Receptor Agonists: A Pharmacovigilance Study Using the FDA Adverse Event Reporting System, Cureus

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A higher proportion of women participate in weight-loss clinical trials.

    “However, a higher proportion of women participate in weight-loss clinical trials [106].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [106] Muscogiuri, 2024, Obesity: A gender-view, J. Endocrinol. Investig. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The loss of lean body mass during weight loss may be an issue in people already affected by sarcopenic obesity or older patients at risk of age-related sarcopenia, potentially leading to frailty, disability, and loss of autonomy.

    “The loss of LBM (including muscle mass) during weight loss may be an issue in people already affected by sarcopenic obesity or older patients who are at risk of agerelated sarcopenia, potentially leading to frailty, disability, and loss of autonomy [119]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [119] Phillips, 2016, Protein “requirements” beyond the RDA: Implications for optimizing health, Appl. Physiol. Nutr. Metab. source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The 2024 meta-analysis suggested that approximately 30% of weight loss was lean body mass; data were insufficient for analysis of other parameters.

    “The meta-analysis suggested that approximately 30% of weight loss was LBM; data were insufficient for analysis of other parameters [118].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [118] Beavers, 2025, GLP1Ra-based therapies and DXA-acquired musculoskeletal health outcomes: A focused meta-analysis of placebo-controlled trials, Obesity source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both treatment doses and adherence are often lower in RWE studies, which can reduce the incidence of AEs.

    “Furthermore, both treatment doses and adherence are often lower in RWE studies, which can reduce the incidence of AEs [12,[68][69][70].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [12,[68][69][70]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A recent US pharmacovigilance study, not captured in our systematic searches, highlights an increased risk of mortality and serious AEs for some treatments and certain patient groups.

    “as demonstrated by the recent publication of a US pharmacovigilance study, not captured in our systematic searches [122], which highlights an increased risk of mortality and serious AEs for some treatments and certain patient groups.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [122] Bhattacharyya, 2024, Mortality and Serious Adverse Events Associated with Glucagon-Like Peptide-1 Receptor Agonists: A Pharmacovigilance Study Using the FDA Adverse Event Reporting System, Cureus

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Sustainable weight loss is the primary goal of patients taking IBTs.

    “While sustainable weight loss is the primary goal of patients taking IBTs [2]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Tak, 2021, Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand?, Curr. Obes. Rep. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Rapid weight loss can result in a reduction in bone mineral density.

    “Rapid weight loss can also result in a reduction in bone mineral density [116]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [116] Hunter, 2014, Weight loss and bone mineral density, Curr. Opin. Endocrinol. Diabetes Obes. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A number of reviews on similar topics have been previously published, focusing on efficacy or case reports, being narrative reviews, or including a much smaller sample of studies.

    “A number of reviews on similar topics have also been previously published [124-128], focusing on efficacy [125] or case reports [126], being narrative reviews [127,128], or including a much smaller sample of studies [124].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [124] Moiz, 2025, Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss Among Adults Without Diabetes: A Systematic Review of Randomized Controlled Trials, Ann. Intern. Med. source

      Not checked in the free run.

    • cites [125] Vosoughi, 2021, Association of glucagon-like peptide 1 analogs and agonists administered for obesity with weight loss and adverse events: A systematic review and network meta-analysis, eClinicalMedicine source

      Not checked in the free run.

    • cites [126] Shetty, 2022, Adverse drug reactions of GLP-1 agonists: A systematic review of case reports, Diabetes Metab. Syndr. Clin. Res. Rev. source

      Not checked in the free run.

    • cites [127] Moore, 2023, GLP-1 Agonists for Weight Loss: Pharmacology and Clinical Implications, Adv. Ther. source

      Not checked in the free run.

    • cites [128] Tobaiqy, 2024, A review of serious adverse events linked with GLP-1 agonists in type 2 diabetes mellitus and obesity treatment, Pharmacol. Rep. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    Although a date restriction of 2014 onwards could be considered a limitation, given the relatively recent approval of incretin mimetics for the treatment of obesity, this is unlikely to have introduced any meaningful bias into our findings.

    “Although a date restriction of 2014 onwards could be considered a limitation, given the relatively recent approval of incretin mimetics for the treatment of obesity, this is unlikely to have introduced any meaningful bias into our findings.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The AEs collated by Shetty et al., 2022, from case reports, primarily include GI, renal, and hepatic events, but also found dermatologic and immunologic events.

    “The AEs collated by Shetty et al., 2022 [126], from case reports, primarily include GI, renal, and hepatic events, but also found dermatologic and immunologic events”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [126] Shetty, 2022, Adverse drug reactions of GLP-1 agonists: A systematic review of case reports, Diabetes Metab. Syndr. Clin. Res. Rev. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The work by Vosoughi et al., 2021, highlighted dulaglutide and exenatide, neither of which were included in our review, as being associated with the highest discontinuation rates due to AEs (based on 64 studies).

    “The work by Vosoughi et al., 2021 [125], highlighted dulaglutide and exenatide, neither of which were included in our review, as being associated with the highest discontinuation rates due to AEs (based on 64 studies)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [125] Vosoughi, 2021, Association of glucagon-like peptide 1 analogs and agonists administered for obesity with weight loss and adverse events: A systematic review and network meta-analysis, eClinicalMedicine source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Meta-analyses of the efficacy and safety of individual IBTs (liraglutide and semaglutide) and of tirzepatide compared with semaglutide have also previously been published.

    “Meta-analyses of the efficacy and safety of individual IBTs (liraglutide [seven studies] and semaglutide [four studies]) and of tirzepatide compared with semaglutide (twenty-eight studies) have also previously been published [129][130][131].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [129][130][131]

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The data identified in this review should not be applied to the use of these therapies in the management of T2DM, given that the dosing in the obesity indication is approximately twice as high as that in the T2DM indication.

    “The data identified in this review should not be applied to the use of these therapies in the management of T2DM, given that the dosing in the obesity indication is approximately twice as high as that in the T2DM indication.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The dosing in the obesity indication is approximately twice as high as that in the T2DM indication.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    This lack of data on dietary intake quality and adequacy in patients with obesity who are taking IBTs has also been highlighted by a recent review, raising concerns around the potential loss of muscle mass and micronutrient deficiencies.

    “This lack of data on dietary intake quality and adequacy in patients with obesity who are taking IBTs has also been highlighted by a recent review, raising concerns around the potential loss of muscle mass and micronutrient deficiencies [110].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [110] Christensen, 2024, Dietary intake by patients taking GLP-1 and dual GIP/GLP-1 receptor agonists: A narrative review and discussion of research needs, Obes. Pillars source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationnone given

    Excluded studies also included those with <50 patients, which could have introduced a greater degree of variability and reduced the generalizability of our findings.

    “Excluded studies also included those with <50 patients, which could have introduced a greater degree of variability and reduced the generalizability of our findings.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Our review included both populations with and without T2DM, and was not designed to evaluate any differences in the AE profile between them.

    “Our review included both populations with and without T2DM, and was not designed to evaluate any differences in the AE profile between them.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Strengths of our analysis include the robust, predefined methodology, conforming to published guidelines issued by the Cochrane Collaboration guidelines.

    “Strengths of our analysis include the robust, predefined methodology, conforming to published guidelines issued by the Cochrane Collaboration guidelines.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Differences in AE incidence between the treatment arms were generally not statistically analyzed.

    “Differences in AE incidence between the treatment arms were generally not statistically analyzed.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A non-systematic review by Tobaiqy et al., 2024, did not allow the authors to draw any firm conclusions, given the mixed results of the included trials.

    “A non-systematic review by Tobaiqy et al., 2024 [128] did not allow the authors to draw any firm conclusions, given the mixed results of the included trials.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [128] Tobaiqy, 2024, A review of serious adverse events linked with GLP-1 agonists in type 2 diabetes mellitus and obesity treatment, Pharmacol. Rep. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    The majority of previous publications focus on efficacy and cost-effectiveness.

    “The majority of previous publications focus on efficacy and cost-effectiveness.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Vosoughi et al. also noted nausea and vomiting as common side effects for all agents evaluated.

    “they also noted nausea and vomiting as common side effects for all agents evaluated.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [125] Vosoughi, 2021, Association of glucagon-like peptide 1 analogs and agonists administered for obesity with weight loss and adverse events: A systematic review and network meta-analysis, eClinicalMedicine source

      Not checked in the free run.

99 of 99

  • The paper relies on this without support.

    As with any other medication, it is to be expected that the incidence of AEs will be dose-dependent.

    “As with any other medication, it is to be expected that the incidence of AEs will be dose-dependent.”

  • The paper relies on this without support.

    The dosing in the obesity indication is approximately twice as high as that in the T2DM indication.

    “given that the dosing in the obesity indication is approximately twice as high as that in the T2DM indication.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In a second systematic literature review involving more than 400,000 patients with obesity and/or T2DM treated with liraglutide, semaglutide or tirzepatide, GI adverse events were the most common with placebo-adjusted incidence ranges of 5-43% for nausea, -7-39% for diarrhea, 2-31% for constipation, 0-26% for vomiting, and 2-20% for abdominal pain.

    “GI adverse events were again the most common with placebo-adjusted incidence ranges of 5–43 % for nausea, -7–39 % for diarrhea, 2–31 % for constipation, 0–26 % for vomiting, and 2–20 % for abdominal pain [47].”

    From Application of nutrition interventions with GLP-1 based therapies: A narrative review of the challenges and solutions (2025) · cites this paper as [47]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Semaglutide fat-mass treatment difference does not match the arm changes

    Major

    The table reports fat-mass changes of −8.36 kg with semaglutide and −1.37 kg with placebo. Their difference is −6.99 kg, not the reported fat-mass estimated treatment difference of −3.3.

    Reported -3.3 · recomputed -6.99

  • Semaglutide lean-body-mass treatment difference does not match the arm changes

    Major

    The table reports changes of −5.26 kg with semaglutide and −1.83 kg with placebo. Their difference is −3.43 kg, not the reported lean-body-mass estimated treatment difference of −7.0.

    Reported -7 · recomputed -3.43

  • Abstract understates the maximum placebo-adjusted nausea incidence

    Minor

    The abstract gives a maximum of 39%, but the results give 43.3% for liraglutide in clinical studies.

  • Discussion understates placebo-adjusted abdominal-pain incidence

    Minor

    The discussion says abdominal pain was reported at 0-10% after placebo adjustment, whereas the results give maxima of 20%, 16.6%, and 14.3% for the three therapies.

  • Diabetes-status categories total 88, not 81 publications

    Minor

    The listed categories contain 13 + 3 + 25 + 40 + 7 = 88 publications, although the review says it included 81. The phrase "remaining seven" is inconsistent with the preceding counts already totaling 81.

    Reported 81 · recomputed 88

5 of 5

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Related

Authors
Kushner, R. F., Johansen, O. E., Araujo Torres, K., Phan, T.-M., & Marczewska, A.
Affiliations
  • Northwestern University (US)
  • Nestlé (Switzerland) (CH)
  • Nestlé Health Science, Bridgewater, NJ 08807, USA
  • Nestlé Health Science, 1800 Vevey, Switzerland
Corresponding author
Marczewska, Agnieszka
ORCID
Venue
Obesities
Publisher
MDPI AG
Published
2025-04-24
Volume
5
Issue
2
Pages
29
ISSN
2673-4168 (ISSN-L)
DOI
10.3390/obesities5020029
OpenAlex
W4409766316
Cited by
5
References
126
Citations by year
2026: 4 · 2025: 1
FWCI
0.68
Type
journal article
Language
en
Open access
Licence
Locations
  • Obesities (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Nestlé Health Science
Topics
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
Keywords
incretin-based therapy, obesity, liraglutide, semaglutide, tirzepatide, adverse events, gastrointestinal adverse effects, nausea, diarrhea, constipation, vomiting, abdominal pain, quality of life, patient-reported outcomes, dose escalation, anti-obesity drugs

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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