Association of semaglutide with less limb events in people with type 2 diabetes and peripheral artery disease or foot ulcers: An observational study comparing matched cohorts

Diabetes Obes Metab. 2025 Oct;27(10):5506-5513. doi: 10.1111/dom.16594. Epub 2025 Jul 7.

Abstract

Aims: To compare major limb events in individuals with type 2 diabetes who initiated either injective or oral semaglutide versus other glucose-lowering therapies (GLT) in a real-world setting.

Materials and methods: This was a single-centre retrospective observational study on new users of diabetes medications. Participants had to have type 2 diabetes and a diagnosis of peripheral artery disease (PAD) or foot ulcers. Participant characteristics were assessed before and after propensity score matching. The primary outcome was major limb events (a composite of peripheral percutaneous transluminal angioplasty [PTA] or critical limb ischaemia [CLI]); secondary outcomes included singularly PTA, CLI, gangrene and lower extremity amputation (LEA).

Results: We analysed two matched groups of 167 participants each, who were predominantly males (57%), aged 61 years, with a 12-year duration of diabetes, a baseline HbA1c of 8.0% and body mass index (BMI) of 31 kg/m2. During a median follow-up of 30.1 months, a primary-outcome event occurred in 72 of the participants (43.0%; incidence, 8.1 events per 100 person-years) in the semaglutide group, as compared with 93 of the participants (56.0%; incidence, 10.4 events per 100 person-years) in the GLT group (hazard ratio [HR] = 0.77; 95% confidence interval [CI], 0.61-0.97; p = 0.029). Among the secondary outcomes, LEA (both major and minor) was 50% lower (HR = 0.50; 95% CI, 0.30-0.83, p = 0.008) in the semaglutide group as compared with the other group.

Conclusions: Among people with type 2 diabetes and PAD or foot ulcers, the use of semaglutide was associated with a significantly lower risk of major limb events than other GLTs.

Keywords: critical limb ischaemia; gangrene; lower limb amputations; peripheral artery disease; peripheral percutaneous transluminal angioplasty; real‐world; semaglutide; type 2 diabetes.

Publication types

  • Observational Study
  • Comparative Study

MeSH terms

  • Aged
  • Amputation, Surgical / statistics & numerical data
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetic Foot* / complications
  • Diabetic Foot* / epidemiology
  • Diabetic Foot* / prevention & control
  • Female
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides* / administration & dosage
  • Glucagon-Like Peptides* / therapeutic use
  • Humans
  • Hypoglycemic Agents* / administration & dosage
  • Hypoglycemic Agents* / therapeutic use
  • Male
  • Middle Aged
  • Peripheral Arterial Disease* / complications
  • Peripheral Arterial Disease* / epidemiology
  • Retrospective Studies
  • Semaglutide
  • Treatment Outcome

Substances

  • Glucagon-Like Peptides
  • Hypoglycemic Agents
  • Glucagon-Like Peptide 1
  • Semaglutide