Trial reportDiabetes care2025
High-Dose Semaglutide (Up to 16 mg) in People With Type 2 Diabetes and Overweight or Obesity: A Randomized, Placebo-Controlled, Phase 2 Trial.
Trial report in Diabetes care, 2025. The graph read 4 numbers from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. Cited by 10 papers, 1 of them a synthesis 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.
Read, but not usablea number the graph found but could not read as for or against
RESULTS: Estimated treatment difference between 16 and 2 mg was -0.3 percentage points (%-points) (95% CI -0.7 to 0.2; P = 0.245) for HbA1c change and -3.4 kg (-6.0 to -0.8; P = 0.011) for weight change for the treatment policy estimand and -0.5%-points (-1.0 to -0.1; P = 0.015) and -4.5 kg (-7.6 to -1.4; P = 0.004), respectively, for the hypothetical estimand.
RESULTS: Estimated treatment difference between 16 and 2 mg was -0.3 percentage points (%-points) (95% CI -0.7 to 0.2; P = 0.245) for HbA1c change and -3.4 kg (-6.0 to -0.8; P = 0.011) for weight change for the treatment policy estimand and -0.5%-points (-1.0 to -0.1; P = 0.015) and -4.5 kg (-7.6 to -1.4; P = 0.004), respectively, for the hypothetical estimand.
RESULTS: Estimated treatment difference between 16 and 2 mg was -0.3 percentage points (%-points) (95% CI -0.7 to 0.2; P = 0.245) for HbA1c change and -3.4 kg (-6.0 to -0.8; P = 0.011) for weight change for the treatment policy estimand and -0.5%-points (-1.0 to -0.1; P = 0.015) and -4.5 kg (-7.6 to -1.4; P = 0.004), respectively, for the hypothetical estimand.
RESULTS: Estimated treatment difference between 16 and 2 mg was -0.3 percentage points (%-points) (95% CI -0.7 to 0.2; P = 0.245) for HbA1c change and -3.4 kg (-6.0 to -0.8; P = 0.011) for weight change for the treatment policy estimand and -0.5%-points (-1.0 to -0.1; P = 0.015) and -4.5 kg (-7.6 to -1.4; P = 0.004), respectively, for the hypothetical estimand.
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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.
GLP-1 receptor agonists×glycemic control
No readable resultOpen on the map →What to test next →40 readable studies in this cell: 96 favour the treatment, 17 find no difference, 10 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×body weight & composition
No readable resultOpen on the map →What to test next →40 readable studies in this cell: 83 favour the treatment, 15 find no difference, 11 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
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Dose-Escalation Regimens for Incretin Mimetics in Type 2 Diabetes Are Associated With Tolerance for Nausea and Vomiting.Diabetes, obesity & metabolism · 2026Pooled it
- The evolving landscape of obesity pharmacotherapy.Nature reviews. Drug discovery · 2026Review
- Estimated Oral Semaglutide Exposure Has Distinct Relationships With Glycaemic Response, Weight Loss and Gastrointestinal Tolerability.Diabetes, obesity & metabolism · 2026Article
- The science of safety: adverse effects of GLP-1 receptor agonists as glucose-lowering and obesity medications.The Journal of clinical investigation · 2026Review
- The expanding landscape of GLP-1 medicines.Nature medicine · 2026Review
- Position Statement on Cardiometabolic Health Across the Woman's Life Course - 2025.Arquivos brasileiros de cardiologia · 2025Article
- Low Dose GLP-1 Therapy Attenuates Pathological Cardiac and Hepatic Remodelling in HFpEF Independent of Weight Loss.bioRxiv : the preprint server for biology · 2025Article
- Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity:European heart journal open · 2025Article
- Development of a risk prediction model for gastrointestinal adverse events associated with semaglutide administration in patients with type 2 diabetes mellitus.Frontiers in endocrinology · 2025Article
- Position Statement on Cardiometabolic Health Across the Woman's Life Course - 2025.Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia · 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
7 authors.
Funding
Abstract
The marked sentences are the ones the graph read a number from.
objectiveStudies have demonstrated dose-dependent efficacy of glucagon-like peptide 1 receptor agonists for glycemic control and body weight. The aim of this trial was to characterize the dose-dependent effects of semaglutide (up to 16 mg/week) in people with type 2 diabetes and overweight or obesity. RESEARCH DESIGN AND
methodsIn this parallel-group, participant- and investigator-blinded, phase 2 trial, 245 individuals with type 2 diabetes and BMI ≥27 kg/m2 on metformin were randomized to weekly semaglutide (2, 8, or 16 mg s.c.) or placebo for 40 weeks. Doses were escalated every 4 weeks, followed by a maintenance period. Dose modifications were not allowed. Primary and secondary efficacy end points included change from baseline to week 40 in HbA1c and body weight, respectively.
resultsEstimated treatment difference between 16 and 2 mg was -0.3 percentage points (%-points) (95% CI -0.7 to 0.2; P = 0.245) for HbA1c change and -3.4 kg (-6.0 to -0.8; P = 0.011) for weight change for the treatment policy estimand and -0.5%-points (-1.0 to -0.1; P = 0.015) and -4.5 kg (-7.6 to -1.4; P = 0.004), respectively, for the hypothetical estimand. Dose-response modeling confirmed these findings. Treatment-emergent adverse events (AEs) and treatment discontinuations due to AEs, primarily gastrointestinal, were more frequent in the semaglutide 8 and 16 mg groups than in the 2 mg group. No severe hypoglycemic episodes were reported.
conclusionsHigher semaglutide doses for type 2 diabetes and overweight or obesity provide modest additional glucose-lowering effect, with additional weight loss, at the expense of more AEs and treatment discontinuations. A study for evaluating high-dose semaglutide in obesity is currently underway.
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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.