SynthesisAnnals of Saudi medicine
Gastrointestinal safety of semaglutide and tirzepatide vs. placebo in obese individuals without diabetes: a systematic review and meta analysis.
Synthesis in Annals of Saudi medicine. The graph read 3 numbers from its abstract, feeding 2 cells of the map: it supports the treatment in 2. Cited by 13 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
RESULTS: Overall GI adverse events were 1.86 times higher with *both* agents (95% CI=1.56, 2.21), with tirzepatide showing a greater risk (RR 2.94, 95% CI=2.61, 3.32) than semaglutide (RR 1.68, 95% CI=1.46, 1.94).
RESULTS: Overall GI adverse events were 1.86 times higher with *both* agents (95% CI=1.56, 2.21), with tirzepatide showing a greater risk (RR 2.94, 95% CI=2.61, 3.32) than semaglutide (RR 1.68, 95% CI=1.46, 1.94).
RESULTS: Overall GI adverse events were 1.86 times higher with *both* agents (95% CI=1.56, 2.21), with tirzepatide showing a greater risk (RR 2.94, 95% CI=2.61, 3.32) than semaglutide (RR 1.68, 95% CI=1.46, 1.94).
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Where it lands on the map
Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.
What it adds to each cell
For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.
GIP/GLP-1 & amylin agonists×adverse events & safety
SupportsOpen on the map →What to test next →4 readable studies in this cell: 2 favour the treatment, 2 find no difference, 0 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
GLP-1 receptor agonists×adverse events & safety
SupportsOpen on the map →What to test next →40 readable studies in this cell: 45 favour the treatment, 14 find no difference, 2 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Dietary Strategies and Nutritional Management in Patients Receiving GLP-1 and Dual GIP/GLP-1 Receptor Agonists as Adjuncts to Lifestyle Interventions: A Systematic Review of Randomised Clinical Trials.Diabetes, obesity & metabolism · 2026Pooled it
- GLP-1 Receptor Agonists and Noncardiometabolic Outcomes: An Umbrella Review of Meta-Analyses.JAMA network open · 2026Pooled it
- A systematic review of semaglutide-associated kidney injury case reports.Frontiers in medicine · 2026Pooled it
- Glucagon-like peptide-1 receptor agonists and pancreatic outcomes in chronic pancreatitis: a real-world cohort study.BMC gastroenterology · 2026Article
- Beyond GLP-1 Agonists: Plant-Derived Bioactive Compounds as Adjunctive Strategies for Obesity Management.Nutrients · 2026Review
- Differential Anti-Inflammatory Effects of Semaglutide and Tirzepatide in Experimental Diabetes Mellitus.Current issues in molecular biology · 2026Article
- Peptide Hormones in Appetite Regulation: A Complex Network.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Incretin-Based Drugs for Obesity: Common and Drug-Specific Reporting Patterns of Adverse Drug Reactions-A Comparative Disproportionality Analysis Using EudraVigilance Reports Integrating SmPC Data.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Real-World Comparison of Short-Term Adverse Events, Treatment Persistence, and Efficacy of Semaglutide and Tirzepatide: A Nationwide Multicenter Study.Obesity facts · 2026Article
- Effectiveness, safety, and treatment patterns of GLP-1 receptor agonists in adolescents with obesity: a multicenter retrospective study from Saudi Arabia.Frontiers in nutrition · 2026Article
- A Comprehensive Analysis of Dermatological Manifestations in Lower Limb Para-Athletes.Archives of clinical and medical case reports · 2026Article
- Gastrointestinal Adverse Effects of GLP-1 and Dual GLP-1/GIP Receptor Agonists: A Comprehensive Update in Diabetic and Obese Populations.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- A Critical Analysis of the Clinical Use of Incretin-Based Therapies: Efficacy and Adverse Events.Archives of clinical and medical case reports · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
introductionSemaglutide and tirzepatide are newly approved glucagon-like peptide-1 receptor agonists for weight management in adults without diabetes. However, safety concerns regarding gastrointestinal (GI) adverse outcomes have been raised. This review comprehensively evaluates their GI safety profile in randomized controlled trials (RCTs).
methodsThirteen RCTs involving 26 894 obese participants without diabetes were analyzed. Pooled analysis assessed the risks for GI, biliary, hepatic, and pancreatic adverse events.
resultsOverall GI adverse events were 1.86 times higher with *both* agents (95% CI=1.56, 2.21), with tirzepatide showing a greater risk (RR 2.94, 95% CI=2.61, 3.32) than semaglutide (RR 1.68, 95% CI=1.46, 1.94). Semaglutide increased gallbladder-related disorders, particularly cholelithiasis, by over 2.6 times (95% CI=1.40, 4.82), while tirzepatide showed no significant biliary risk. Neither agent significantly increased hepatic or pancreatic adverse events.
conclusionCompared to placebo, both Semaglutide and tirzepatide are associated with increased GI adverse outcomes, with most cases being mild. Clinicians should carefully monitor patients for potential adverse outcomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.