Liraglutide for Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease: The STARDUST Randomized Clinical Trial
- Design
- Randomized trial · 24 participants · Mixed outcome
- Match to healthy normal-weight adults aged 55–75
- Different population[Auto] Participants had type 2 diabetes (age/BMI not reported in abstract).
- Could weight loss explain it?
- Possibly[Auto] Participants had obesity and/or type 2 diabetes and the abstract does not separate direct drug effects from weight loss or glycaemic improvement.
- Study tier
- Study tier 3[Auto] Small or short randomized trial (auto-provisional).
- Assessment
- Version 1 · automatic, not yet reviewed by a person · Sep 13, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
[Auto, unreviewed; quoted from abstract conclusions] In this randomized clinical trial of people with type 2 diabetes and PAD, liraglutide increased peripheral perfusion detected by TcPo2 measurement during 6 months of treatment. These results support the use of liraglutide to prevent the clinical progression of PAD in individuals with type 2 diabetes.
01Findings
What the study reported
- Drugs
- Liraglutide
- Dose
- 1.8 mg
- Treatment duration
- 6 months
- Route
- subcutaneous
- Comparator
- the control group
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- 6 months
- Adverse events
- Not extracted
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Diabetes status
- type 2 diabetes present (all or most)
- Sample size
- 24
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 24
- Randomization
- yes
- Blinding
- open-label
- Comparator
- not stated
- Follow up duration
- 6 months
- Outcome type
- mixed
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 95% CI, 8
- Funding conflicts
- unclear
- Peer review status
- yes
01bRisk of bias
How much the result can be relied on
Risk of bias is judged per result, not per paper: the same study can report one marker at low risk and another at high. Two reviewers assess each result independently against a written guide, and every domain judgment below carries its reasoning and the sentences it rests on.
These words are not quality scores. On the RoB 2 scale, High risk of bias is the worst rating a result can receive and Low risk of bias is the best — the opposite of how the same words read on some other scales. Levels are always written out in full here for that reason.
C-reactive protein (CRP), change from baseline, liraglutide vs conventional treatment · 6 months
Some concerns about risk of bias · RoB 2 · Two reviewers agreed on every domain
How the overall was reached: No domain is High. D1, D3 and D4 are Low on retrieved evidence. D2 is Some concerns (open-label with no placebo, unequal background-therapy changes, completers-only analysis of 55/60 randomized), and D5 is Some concerns (prespecification of the CRP analysis unverifiable, no multiplicity adjustment). Per the RoB 2 algorithm, some concerns in at least one domain with none High gives an overall judgment of Some concerns.
| Domain | Judgment and reasoning |
|---|---|
| D1 · Randomisation process Low risk of bias | Sequence generation and allocation concealment are explicitly described in the retrieved full text, so D1 rests on verification rather than on any presumption. Per rule 4 of this task and guide item 6, the large-industry presumption does not apply to this small single-centre academic trial and is not invoked. Baseline characteristics (Table 1) are balanced, with no imbalance suggesting a problem.Randomization was performed by a computer-generated random number sequence. Allocation was concealed in study folders that were held in a central location until after informed consent was obtained. Participants who met eligibility were randomly assigned to liraglutide subcutaneous daily injection or a matching control group for the duration of the study. |
| D2 · Deviations from intended interventions Some concerns about risk of bias | The trial is open-label with no placebo, so participants and treating staff knew assignment. Per the guide, awareness alone rarely biases a lab biomarker, so the judgment rests on co-interventions, discontinuation imbalance and ITT handling. Background glucose-lowering therapy was changed in a large share of both arms (67% liraglutide vs 78% control), with lipid-lowering changes also unequal (22% vs 32%); these are protocol-permitted standard-of-care co-interventions in both arms rather than deviations arising from awareness, and the authors state the groups did not differ in risk-factor management, but the imbalance is unequal and unadjusted, and statin changes can move CRP. Withdrawal was small and near-equal (3/30 vs 2/30). The analysis excluded all 5 non-completers, so it is not an ITT analysis; no ITT or sensitivity analysis is reported. Not High, because the exclusions are few and balanced and the co-interventions were applied to both arms by design.The numbers of participants in the liraglutide group who underwent changes (dose and/or molecule) of current treatments were 18 (67%) for glucose-lowering, 6 (22%) for lipid-lowering, 6 (22%) for antihypertensive, and 4 (15%) for antiplatelet or anticoagulant medications. In the control group, changes of current therapies occurred in 22 (78%) for glucose-lowering, 9 (32%) for lipid-lowering, 6 (21%) for antihypertensive, and 5 (18%) for antiplatelet or anticoagulant drugs. Individuals in both groups were given, if needed, tailored therapeutic prescriptions to manage blood glucose levels and cardiovascular risk factors, according to the standards of medical care. |
| D3 · Missing outcome data Low risk of bias | Outcome data are available for 55 of 60 randomized participants (91.7%). Missingness is 10.0% (3/30) in the liraglutide arm and 6.7% (2/30) in the control arm: below the guide's 20% threshold and a 3.3-point arm difference, below the 5-point threshold. Neither prong trips, so per calibration ruling 2 D3 is Low; the absence of an MNAR sensitivity analysis is recorded in limitations, not as a downgrade.Sixty individuals met the inclusion criteria and underwent randomization: 30 participants were assigned to the liraglutide group and 30 to the control group. Three individuals from the liraglutide group and 2 in the control group withdrew from the study and/or were lost during follow-up |
| D4 · Measurement of the outcome Low risk of bias | CRP is an objective laboratory assay. The outcome assessors and laboratory staff were masked to allocation, and no assay change or between-arm measurement difference is reported. Per the guide, measurement bias for central-lab CRP is Low absent such evidence.the laboratory staff did not know the patients’ group assignments. The trial staff who assessed outcomes and analyzed the data were masked to group assignment. The open-label design could have introduced some biases, although investigators who evaluated the outcomes were blinded to the treatment allocation. |
| D5 · Selection of the reported result Some concerns about risk of bias | CRP is named in the paper's own list of prespecified secondary outcomes, and the trial is registered (NCT04881110) with a trial protocol posted as Supplement 1. But under guide item 7 the paper's own prespecification claim is not verification: neither the protocol, the supplement nor the registry entry was retrievable in this bundle (only the supplement titles appear), so prespecification is unverified and D5 sits at the "at least Some concerns" floor. No author statement labels the CRP analysis post hoc or exploratory (the "exploratory" label is attached specifically to the 6MWT), so the High trigger in item 7 does not fire. Weighing against Low: many secondary outcomes are reported with no multiplicity adjustment stated, and CRP is presented in two framings (a within-group change P < .001 and the between-group difference P = .02).Additional secondary outcomes were glycemic and metabolic parameters (HbA 1c , weight, body mass index [calculated as weight in kilograms divided by height in meters squared], and systolic and diastolic blood pressure), lipid profile (total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, and triglycerides), C-reactive protein (CRP), kidney function parameters The STARDUST protocol also included assessment of 6MWT as an exploratory outcome. |
Assessed, not settled (1)
Recorded rather than omitted. Leaving these out would make the appraisal look cleaner than it is, and a disagreement between two careful readers is itself worth knowing.
Interleukin 6 (IL-6), change from baseline, liraglutide vs conventional treatment · 6 months
Assessed, not settled · RoB 2 · Two reviewers reached different judgments and nothing has settled it
This result has no overall judgment, because the two independent reviews did not reach one. Both readings are shown. The domains they did agree on are below.
| Where they differ | The two readings |
|---|---|
| D3 · Missing outcome data | One reviewer: Some concerns about risk of bias The other: Low risk of bias |
| Domain | Judgment and reasoning |
|---|---|
| D1 · Randomisation process Low risk of bias | Same trial-level randomization as O1; verified from the retrieved full text, not presumed.Randomization was performed by a computer-generated random number sequence. Allocation was concealed in study folders that were held in a central location until after informed consent was obtained. |
| D2 · Deviations from intended interventions Some concerns about risk of bias | Identical considerations to O1: open-label without placebo, unequal and substantial changes in background glucose-lowering and lipid-lowering therapy in both arms, and a completers-only analysis rather than ITT. Awareness alone is not weighted for a lab biomarker per the guide.The numbers of participants in the liraglutide group who underwent changes (dose and/or molecule) of current treatments were 18 (67%) for glucose-lowering, 6 (22%) for lipid-lowering, 6 (22%) for antihypertensive, and 4 (15%) for antiplatelet or anticoagulant medications. In the control group, changes of current therapies occurred in 22 (78%) for glucose-lowering, 9 (32%) for lipid-lowering, 6 (21%) for antihypertensive, and 5 (18%) for antiplatelet or anticoagulant drugs. This open-label randomized clinical trial was conducted between February 1, 2021, and June 30, 2022 |
| D3 · Missing outcome data Some concerns about risk of bias | Trial-level attrition is 5/60 (10.0% vs 6.7%), below both guide thresholds. But the IL-6 denominator is never reported: the result is given only in a narrative sentence referring to eTable 4, which was not retrievable, and no flow information confirms that IL-6 samples were available for all 55 completers. The guide notes biomarker substudies often have uncollected samples. With the analysed n unverifiable, this is not Low on the evidence.Compared with the control group, individuals assigned to the liraglutide group had a significant reduction in levels of CRP (difference, −0.4 mg/dL; 95% CI, −0.7 to −0.07 mg/dL; P = .02) (eFigure 2 in Supplement 2 ), interleukin 6 (difference, −31.6; 95% CI, −54.6 to −8.7; P = .008) Three individuals from the liraglutide group and 2 in the control group withdrew from the study and/or were lost during follow-up |
| D4 · Measurement of the outcome Low risk of bias | IL-6 is an objective laboratory assay; laboratory staff were blinded to assignment and no assay change or between-arm measurement difference is reported.the laboratory staff did not know the patients’ group assignments. The trial staff who assessed outcomes and analyzed the data were masked to group assignment. |
| D5 · Selection of the reported result High risk of bias | IL-6 differs from CRP here and is judged separately. It is NOT in the paper's own enumerated list of secondary outcomes in Methods (which names CRP explicitly), and it appears only in the Results as one of a cluster of markers reported in eTable 4 with no stated units and no multiplicity adjustment. That absence from the paper's own list is a real concern about selective reporting. It does not reach High under guide item 7, however: ruling 3's High requires a fully searchable protocol showing affirmative absence, and no author statement calls the IL-6 analysis post hoc, exploratory, or unadjusted. The protocol (Supplement 1) and registry entry were not retrievable, so the "at least Some concerns" floor applies. This is Some concerns at the upper end.Additional secondary outcomes were glycemic and metabolic parameters (HbA 1c , weight, body mass index [calculated as weight in kilograms divided by height in meters squared], and systolic and diastolic blood pressure), lipid profile (total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, and triglycerides), C-reactive protein (CRP), kidney function parameters (urine albumin to creatinine ratio [UACR], and estimated glomerular filtration rate). interleukin 6 (difference, −31.6; 95% CI, −54.6 to −8.7; P = .008), luteinizing hormone (difference, −1.1 mIU/mL; 95% CI, −2.0 to −0.2 mIU/mL |
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- None identified
- Sponsor role
- not reported in abstract
- Author conflicts
- not available in metadata
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[IMPORTANCE] Peripheral artery disease (PAD) in diabetes may lead to diabetic foot ulcer and lower-extremities amputation. Glucagon-like peptide 1 receptor agonists have proven cardiovascular benefits in trials of people with type 2 diabetes at high cardiovascular risk. [OBJECTIVE] To examine the effect of liraglutide on peripheral perfusion measured as peripheral transcutaneous oxygen pressure (TcPo2) in individuals with type 2 diabetes and PAD. [DESIGN, SETTING, AND PARTICIPANTS] This open-label randomized clinical trial was conducted between February 1, 2021, and June 30, 2022, with a final follow-up on December 30, 2022, at University of Campania "Luigi Vanvitelli," Naples, Italy. Fifty-five individuals with type 2 diabetes, PAD, and TcPo2 between 30 and 49 mm Hg were included. [INTERVENTIONS] Patients were randomized to receive 1.8 mg of subcutaneous liraglutide or conventional treatment of cardiovascular risk factors (control group) for 6 months. [MAIN OUTCOMES AND MEASURES] Coprimary outcomes were the change from baseline of peripheral perfusion between groups and the comparison of the proportion of individuals who reached 10% increase of TcPo2 from baseline in each group. [RESULTS] Fifty-five participants (mean [SD] age, 67.5 [8.5] years; 43 [78%] male) were randomized (27 to the liraglutide group and 28 to the control group) and analyzed. Participants had a median (IQR) hemoglobin A1c level of 6.9% (6.5%-7.8%) and a mean (SD) TcPo2 of 40.3 (5.7) mm Hg. Transcutaneous Po2 increased over time in both groups, with significant differences favoring the liraglutide group after 6 months (estimated treatment difference, 11.2 mm Hg; 95% CI, 8.0-14.5 mm Hg; P < .001). The 10% increase of TcPo2 occurred in 24 participants (89%) in the liraglutide group and 13 (46%) in the control group (relative risk, 1.91; 95% CI, 1.26-2.90; P < .001). Compared with the control group, individuals in the liraglutide group had a significant reduction of C-reactive protein (-0.4 mg/dL; 95% CI, -0.7 to -0.07 mg/dL; P = .02), urinary albumin to creatinine ratio (-119.4 mg/g; 95% CI, -195.0 to -43.8 mg/g; P = .003), and improvement of 6-minute walking distance (25.1 m; 95% CI, 21.8-28.3 m; P < .001). [CONCLUSIONS AND RELEVANCE] In this randomized clinical trial of people with type 2 diabetes and PAD, liraglutide increased peripheral perfusion detected by TcPo2 measurement during 6 months of treatment. These results support the use of liraglutide to prevent the clinical progression of PAD in individuals with type 2 diabetes. [TRIAL REGISTRATION] ClinicalTrials.gov Identifier: NCT04881110.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 38470420 first ingestion |