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Document set current to 30 July 2026
Compound monograph · evidence extract

Semaglutide in peripheral arterial disease with intermittent claudication — evidence extract

The Institute's graded assessment of Semaglutide for peripheral arterial disease with intermittent claudication, with the contributing trials and the domain-by-domain certainty reasoning.

Document identifier
CEI-MN-001/EV-PAD
Series
Evidence extract
Version
1.1
Published
16 Sep 2023
Last reviewed
16 Aug 2024
Next review
16 Aug 2026
Identifier
10.71829/cei.mono.1
Certainty
Moderate
Cycle
2023 Q3

§1Evidence extract: Peripheral arterial disease with intermittent claudication

§1.1Question and anchor outcome

Population
Atherosclerotic obstruction of the lower-limb arteries producing exertional ischaemic symptoms, with objective confirmation by ankle–brachial index or imaging.
Intervention
Semaglutide, subcutaneous once weekly; oral once daily with a permeation enhancer (see separate monograph)
Comparator
As used in each contributing trial; reported per trial rather than pooled across comparator types
Anchor outcome
Maximum walking distance

Additional outcomes the Institute extracts for this indication: Pain-free walking distance; Ankle–brachial index; Major adverse limb events.

§1.2Contributing trials

Table 1. Trials contributing to the assessment of Semaglutide in peripheral arterial disease with intermittent claudication.

TrialPhaseDesignRandomisedDurationYear
STRIDE3Randomised, double-blind, placebo-controlled79252 weeks2025

§1.3Certainty assessment

Certainty assessment by domainDowngrading decision recorded for each certainty domain.Certainty domainNo concernSeriousVery seriousEffect on ratingRisk of biasdowngrade one levelInconsistencyno downgradeIndirectnessno downgradeImprecisionno downgradePublication biasno downgradeTotal downgrading: 1 levelModerate certainty
Figure 2. Domain-by-domain certainty assessment for Semaglutide in peripheral arterial disease with intermittent claudication. The starting rating for a body of randomised evidence is high; each serious concern reduces it by one level and each very serious concern by two.

Table 2. Reasoning recorded against each certainty domain.

DomainRatingReasoning
Risk of biasSeriousAllocation concealment is not described in one contributing report.
InconsistencyNo concernNo serious concern identified in this domain.
IndirectnessNo concernNo serious concern identified in this domain.
ImprecisionNo concernNo serious concern identified in this domain.
Publication biasNo concernNo serious concern identified in this domain.
Overall rating: Moderate certainty. The true effect is likely to be close to the estimate, but there is a possibility that it is substantially different. Further research is likely to have an important impact on confidence in the estimate.

§1.4What this extract does not establish

References cited on this page

References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.

  1. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF. Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine 2021;384(11):989–1002. doi:10.1056/NEJMoa2032183 · PMID 33567185
  2. Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, Rosenstock J, Shimomura I, Viljoen A, Wadden TA, Lingvay I. 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. The Lancet 2021;397(10278):971–984. doi:10.1016/S0140-6736(21)00213-0 · PMID 33667417
  3. Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, Lingvay I, O’Neil PM, Rubino DM, Skovgaard D, Wallenstein SOR, Garvey WT. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: the STEP 3 randomized clinical trial. JAMA 2021;325(14):1403–1413. doi:10.1001/jama.2021.1831 · PMID 33625476

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